Systems, methods, and devices using stretchable or flexible electronics for medical applications

ABSTRACT

System, devices and methods are presented that integrate stretchable or flexible circuitry, including arrays of active devices for enhanced sensing, diagnostic, and therapeutic capabilities. The invention enables conformal sensing contact with tissues of interest, such as the inner wall of a lumen, a nerve bundle, or the surface of the heart. Such direct, conformal contact increases accuracy of measurement and delivery of therapy.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of the following U.S. ProvisionalApplications: Ser. No. 61/121,568 entitled “Endoscopy Device” filed Dec.11, 2008; Ser. No. 61/121,541 entitled “Nerve Bundle Prosthesis” filedDec. 11, 2008; and Ser. No. 61/140,169 entitled “Body Tissue Screener”filed Dec. 23, 2008, the entirety of each of which is incorporatedherein by reference. Further, this application is a continuation-in-partof and claims the benefit of copending U.S. Nonprovisional patentapplication Ser. No. 12/616,922 entitled “Extremely StretchableElectronics” filed Nov. 12, 2009, the entirety of which is incorporatedherein by reference. Nonprovisional patent application Ser. No.12/616,922 is a continuation-in-part of and claims the benefit of U.S.Provisional Application No. 61/113,622 entitled “Extremely StretchableInterconnects” filed on Nov. 12, 2008, the entirety of which isincorporated herein by reference. Also, Nonprovisional patentapplication Ser. No. 12/616,922 is a continuation-in-part of, and claimsthe benefit of copending U.S. Non-Provisional application Ser. No.12/575,008, entitled “Catheter Balloon Having Stretchable IntegratedCircuitry and Sensor Array” filed on Oct. 7, 2009, the entirety of whichis incorporated herein by reference. Nonprovisional application Ser. No.12/575,008 claims priority to U.S. Provisional Application No.61/103,361 entitled “Catheter Balloon Sensor and Imaging Arrays”, filedOct. 7, 2008, the entirety of which is incorporated herein by reference;and U.S. Provisional Application No. 61/113,007 entitled “CatheterBalloon with Sensor and Imaging Array”, filed Nov. 10, 2008 the entiretyof which is incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to systems, apparatuses, and methodsutilizing expandable or stretchable integrated circuitry and sensorarrays on expandable, flexible or stretchable substrates in or onmedical devices.

BACKGROUND OF THE INVENTION

High quality medical sensing and imaging data has become important inthe diagnoses and treatment of a variety of medical conditions includethose related to conditions associated with the digestive system,conditions related to the cardiocirculatory system, injuries to thenervous system, cancer, and the like. Current sensing and therapeuticdevices suffer from various disadvantages due to a lack ofsophistication related to the sensing, imaging, and therapeuticfunctions. One of these disadvantages is that such devices are unable toachieve direct or conformal contact with the part of the body beingmeasured or treated. The inability to achieve direct or conformalcontact of such devices is partially attributable to the rigid nature ofthe devices and accompanying circuitry. This rigidity prevents devicesfrom coming into confirming and/or direct contact with human tissue,which as readily apparent may change shape and size, and may be soft,pliable, curved, and/or irregularly shaped. Such rigidity thuscompromises accuracy of measurements and effectiveness of treatment.Thus, devices, systems and methods, which employ flexible and/orstretchable systems would be desirable.

Examples of areas that are amenable to such flexible and/or stretchableapproaches include, endoscopy, vascular examination and treatment,neurological treatment and examination, and tissue screening.

As an example, endoscopic imaging of the gastrointestinal (GI) tract isessential for effective diagnosis and treatment of a variety of GIdisorders, including inflammations, ulcers, abscesses, and cancerdetection. By way of elaboration, endoscopic imaging capsules may offercertain advantages over traditional endoscopes for a variety reasons:they involve minimal patient discomfort and can image regions along theGI tract that are inaccessible with traditional endoscopes. Allcomponents are encapsulated within an ellipsoid body whose volume mustbe small enough to be swallowed and ingested. Consequently, there is anadded benefit to minimizing the volume of these ingestible capsules.There also are a variety of features, including power storage andimaging quality that can be significantly improved if the spatial layoutof the components within the capsule could be optimized. Additionally,optical imagers in current endoscopic capsules generally have a planargeometry, with the imager aligned with the optical center of the lens.This geometry is subject to intrinsic limitations such as aberrations,peripheral distortion and illumination inhomogeneity. Stretchable and/orflexible circuitry could mitigate some of the disadvantages describedabove with respect to capsule endoscopy, as well as traditionalendoscopic devices.

Spinal cord and other complex brain or nerve injury is a major cause ofdisability, death and suffering, and to date there are few effectivetreatments. As an example, the complexity of the spinal cord, consistingof thousands of nerve fibers and both dark and gray matter, makessurgical repair extremely difficult, with a high degree of additionalirreversible injury. Therefore, much attention has been focused onreducing scarring and stimulating regeneration with pharmaceuticals orstem cells. Bionic solutions have also gained some interest. Experimentshave been conducted on electrical sensing and stimulation of ascendingand descending bundles, demonstrating that electrical impulses can beused to provide some level of function. Separately, there are devices inclinical use which perform electrical stimulation of nerves in and nearthe spine to treat chronic pain, but these are not intended to restorenerve function. Combining the benefits of these existing devices may notgo far enough toward dramatically improving spinal cord therapies due tosome of the limitation mentioned above. Accordingly, there is a need fordynamically configurable and conformable devices, systems, and methodsthat minimize the risk of further injury while providing increasedfunction to the damaged nerves.

Another example where the benefits of flexible/and or stretchabledevices are needed involves tissue screening. While tissue screeningprocedures are of paramount important for early detection, evaluation,and subsequent treatment of cancer, clinical diagnostic methods, such asmammography and ultrasound imaging are expensive and require trainedpersonnel. Thus, almost two-thirds of cancers are initially detected bypalpatory (i.e. tactile sense of touch) self-examination. Palpatoryexamination is a qualitative technique taught to women, for example, asa preclinical test for breast cancer to be conducted at the home. It iswell known that cancerous tissue undergoes significant changes inmechanical properties with respect to healthy tissue. Local lesions inbreast cancer tissue are stiffer by up to 2-fold. Althoughself-examinations of breast tissue have facilitated early detection ofhardened legions, indicative of tumor growth, the qualitative nature ofthese tests makes it difficult to ascertain any quantitative dataimportant to clinicians or to analyze trends over time. Because theself-examination approach generally involves manually detecting thelocation, size, shape, and density of lesions by conforming fingertipsaround the lesion, a device capable of achieving conformal contact withthe tissue of interest that can quantify and record the intrinsicmechanical properties of tissue can have a significant impact on the waybreast cancer screening is currently performed at the home and in theclinical setting as a supplement to mammography and ultrasound.

Finally, detection and treatment of conditions in the cardiovascularsystem would greatly benefit from approaches that increase the qualityof data generated by sensing devices, techniques, and methods.Currently, such sensing techniques devices and methods are greatlylimited by their inability to achieve close, direct, and or conformalcontact with the area of interest. Therefore, gathering data relating tothe electrical, chemical, and other physical activity or condition ofthe tissue is compromised.

Stretchable and/or flexible electronics can mitigate or resolve many ofthe shortcomings described above. Such techniques can be applied to theareas above, or to any area of physiological sensing, medical detection,or medical diagnostics that would be improved by enhanced contact withsensing or therapeutic devices.

SUMMARY OF THE INVENTION

Methods, systems, and devices are disclosed herein which employstretchable/and or flexible circuitry for physiological sensing,detection of health-related parameters, and delivery of therapeuticmeasures. In embodiments, the circuitry is disposed on a stretchable,flexible, expandable, and/or inflatable substrate. In embodiments,circuitry comprises electronic devices, which may be active devices, inelectronic communication with one another and programmed or configuredto generate output and cause an output facility to display such output,deliver therapeutic measures, generate data regarding physiologicalparameters and/or make determinations of a health-related condition.Embodiments of the invention may include a storage facility incommunication with the processing facility. The processing facility maycause at least one of data generated by the active devices and theoutput data to be stored in the storage facility and may generate outputdata related to the stored data. The processing facility may cause atleast one of data generated by the active devices and the output data tobe aggregated and may generate output data related to the aggregateddata.

In embodiments, the methods and systems herein may comprise a neuralprosthesis device. Thus, in an aspect of the invention, methods, devicesand systems include an apparatus that may include a substrate on whichis disposed circuitry that may include an array of recording electrodesfor receiving signals from a plurality of nerve sources when a portionof the electrodes is in electrical contact with the plurality of nervesources and an array of stimulating electrodes; and a processingfacility in electronic communication with the arrays of electrodes, andbeing configured to receive signals from the recording electrodes anddetermine a pattern of stimulation signals to be effected by thestimulating electrodes.

In the aspect mentioned above and in other embodiments, the electricalcontact may comprise physical contact. Further in embodiments, theapparatus may include a multiplexer configured to match the signals fromthe nerve sources and cause the stimulating electrodes to dispatch acorresponding signal to a second plurality of nerves. The apparatus mayinclude a user interface to adjust the pattern of stimulation signals,which may be dynamically configurable.

In embodiments, the substrate is an inflatable body which may be a diskor a balloon.

In the aspect mentioned above, the processing facility is furtherconfigured to generate data related to the electrical conductivity ofthe nerve sources. The processing facility may be in electroniccommunication with an output facility and may cause the output facilityto generate a map based on the data related to the electricalconductivity of the nerve sources.

In the aspect mentioned above and in other embodiments, the circuitrymay be encapsulated with a thin polymer layer. The circuitry may bestretchable up to 300%. The electrodes may located discretely from oneanother. The circuitry may comprise stretchable electrical interconnectswhich may electrically connect the electrodes.

In embodiments, the circuitry may include sensors that may include anyof temperature sensors, contact sensors, light or photo detectors, ultrasound emitters and transceivers, pressure sensors, or the like.

In this aspect mentioned in conjunction with the neural prosthesis andwith respect to other embodiments disclosed herein, the substrate mayinclude a reservoir in communication with the surface of the substrate,and the circuitry may be configured to open valves operable to release adrug contained within the reservoir where the circuitry may cause thevalves to release the drug in a controlled manner.

In other embodiments, the methods and systems herein may comprise aninflatable device for sensing tissues.

Thus, in another aspect of the invention, methods and systems include anapparatus that may include an inflatable substrate on which may bedisposed circuitry that remains functional upon inflation of thesubstrate and may include an array of active devices that may includesensing devices for detecting data indicative of a parameter associatedwith a tissue; and a processing facility in electronic communicationwith the circuitry, receiving data indicative of a parameter associatedwith the tissue; and an output facility in electronic communication withthe processing facility, where the processing facility may be configuredto generate output data associated with the tissue and to cause theoutput facility to generate output data.

In the aspect mentioned above for sensing tissues and in otherembodiments, the processing facility may receive data generated by thesensing devices and produce an image of the tissue. In embodiments, thesensing devices are configured to be in an active matrix which may beoperated by circuitry which may include at least one of an amplifier anda logic circuit. Further, the apparatus may include a multiplexer whichmay be located at the base of a catheter guide wire coupled to thesubstrate which may be a balloon.

In embodiments, the processing facility may be within the circuitry. Inother embodiments, the processing facility may be separate from thecircuitry.

In this aspect mentioned above with respect to sensing tissueparameters, the output data related to the tissue may be a map which mayinclude a map of electrical activity of the tissue. The output data maycomprise data related to temperature heterogeneity present in arterialplaque. Further, the output data may comprise an indication of plaquetype.

In aspects mentioned above and in other embodiments, the circuitry maycomprise a therapeutic facility which may be configured to ablate thetissue. The circuitry may comprise light emitting electronics. Thecircuitry may comprise an array of photodetectors in communication withthe processing facility where the processing facility may be configuredto generate image of the tissue and to cause the output facility tooutput an image which may be high resolution. Where the circuitry isdelivered via a catheter having a guide wire, the guide wire may includea light source, which may be an optical fiber, to provide light to thephotodetectors.

In embodiments, the tissue of interest may include any of a pulmonaryvein, a septal wall of a heart, an atrial surface of a heart, and aventricular surface of a heart.

In another aspect of the invention, methods and systems include a methodof detecting parameters associated with a lumen in the body of anindividual. The method may include inserting an un-inflated ballooncatheter into the lumen, the balloon catheter having a stretchableballoon having stretchable circuitry applied thereto, the stretchablecircuitry comprising sensing devices; directing the sensing devices tobe in an area of interest within the lumen; and inflating the balloonand causing the sensing devices to come into conformal contact withsurface of the area of interest within the lumen.

With respect to embodiments mentioned above and others disclosed herein,the invention may comprise sensing devices to generate data indicativeof a parameter of the area of interest when the sensing devices are inconformal contact with the area of interest. Like other embodiments, thegenerated data may be used to produce any of an image of the area ofinterest and a map of the area of interest where the map may includedata indicative of the electrical activity of the area of interest.

In another aspect of the invention, methods and systems include a methodof detecting parameters associated with a lumen in the body of anindividual. The method may include inserting an un-inflated ballooncatheter into the lumen, the balloon catheter having a stretchableballoon having stretchable circuitry applied thereto, the stretchablecircuitry comprising sensing devices; directing the sensing devices tobe in an area of interest within the lumen; and inflating the balloonand causing the sensing devices to come into partial sensing contactwith surface of the area of interest within the lumen.

In yet an aspect of the invention, methods and systems include a methodof detecting a parameter of a tissue. The method may include placing anarray of active sensing devices in conformal contact with the tissue,the array comprising stretchable circuitry; generating data with thesensing devices; and determining the parameter from the generated data.

The methods and systems herein may comprise a tissue screening device.

Thus, in still yet another aspect of the invention, methods and systemsinclude a tissue screening device, including a stretchable substrateconformable to the contour of an area of interest on a body on which maybe affixed stretchable circuitry which may include an array of activedevices; a processing facility in electronic communication with thearray of active devices; and an output facility in electroniccommunication with the processing facility, wherein the processingfacility may be programmed to generate output data based on datagenerated by the array of active devices and to cause the outputfacility to display the output data.

In this aspect, as with others the substrate may be inflatable. Thesubstrate may be affixed to a bra.

In embodiments, the sensor devices include pressure sensors, which mayinclude an on-off switch coupled to the pressure sensor to indicatewhether the pressure sensor has been activated.

In the tissue screening embodiments and in others mentioned above, theprocessing facility may receive data generated by the ultrasoundemitters and receivers and may produce an image of the tissue.

In embodiments of the invention, the output data comprises a contour mapof the area of interest.

In an aspect of the invention, methods and systems include a method ofexamination for cancerous or suspicious tissue which may includeproviding a subject with a wearable device conforming to an area ofinterest on subject's body, the wearable device comprising a stretchablearray of pressure sensors; exerting a manual force on the wearabledevice sufficient to activate the array of pressure sensors; receivingdata from the pressure sensors; and characterizing the tissue in thearea of interest based on the received data. Further in this aspect,instructing the subject to exert the manual force. In this aspect, thewearable device may be inflatable. In this aspect, the wearable devicemay be affixed to a bra. In embodiments, the wearable device may be asheet.

The methods and systems herein may comprise an endoscopy device.

Thus, in another aspect of the invention, methods and systems include anendoscopic device, including a housing to and within which may bemounted curvilinear circuitry which may include a focal plane arraygenerating visual data; a transmission facility in electroniccommunication with the circuitry configured to wirelessly transmit thevisual data; and an output facility receiving and displaying the visualdata.

In this aspect, the housing may be a capsule. The circuitry,transmission facility, and the output facility may be mounted within thecapsule. In this aspect, the housing may be located at a tip of theendoscopic device. In this aspect, the circuitry further comprises lightemitting electronics. In this aspect, the circuitry may be configured toilluminate select portions of the light emitting electronics. thecircuitry may be affixed to an exterior surface of the housing, or thecircuitry may be affixed to an interior surface of the housing.

Further in embodiments related to endoscopy and with respect to otherembodiments herein, the circuitry may include sensing devices which maybe capable of generating any of data related to enzymatic activity anddata related to chemical activity.

In this embodiment and others herein, the circuitry comprises sensingdevices and a processing facility receiving data from the sensingdevices, the processing facility in electronic communication with theoutput facility. The processing facility may cause the output facilityto display information related to data generated by the sensing devices.

Further in this aspect and others, including a processing facilitywithin the circuitry. Further in this aspect, including a processingfacility separate from the circuitry.

In this aspect, the visual data is an image. In this aspect, the visualdata may be a map.

The methods and systems herein may comprise a dynamically configurablesheet of electronic devices.

Thus, in another aspect of the invention, methods and systems include aconfigurable sheet of electronic devices, a substantially flat substrateon which may be disposed stretchable circuitry containing an array ofelectronic devices in electronic communication with one another; and aprocessing facility capable of polling the array of electronic devicesto determine a first set of information related to the identity andlocation of each electronic device in the array, the processing facilityconfigured to adjust the operation of the array based upon informationrelated to a second set of information related to the identity andlocation of each electronic device in the array. In this aspect, thesecond set of information is received after the circuitry is reshaped,where the reshaping may be caused by cutting the circuitry.

In embodiments, circuitry may include an array of electronic devices mayinclude sensor devices which may generate data of a tissue of interestwhen the sheet is at least one of partial electrical contact and partialconformal contact with the tissue of interest.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will become more fully apparent from the followingdescription and appended claims, taken in conjunction with theaccompanying figures. Understanding that these figures merely depictexemplary embodiments of the present invention they are, therefore, notto be considered limiting of its scope. It will be readily appreciatedthat the components of the present invention, as generally described andillustrated in the figures herein, could be arranged and designed in awide variety of different configurations. Nonetheless, the inventionwill be described and explained with additional specificity and detailthrough the use of the accompanying figures in which:

FIG. 1 is a schematic depiction of embodiments of the invention;

FIG. 2 depicts a buckled interconnection;

FIG. 3 depicts a stretchable electronics configuration withsemiconductor; islands mounted on an elastomeric substrate withstretchable interconnects;

FIG. 4 depicts an extremely stretchable interconnect;

FIG. 5 depicts a raised stretchable interconnect with expandableelastomeric substrate;

FIG. 6 depicts a method for controlled adhesion on an elastomeric stamp;

FIG. 7 depicts an embodiment of the invention wherein stretchablecircuitry is applied to a balloon catheter, in which the ballooncatheter is deflated;

FIG. 7A is a expanded view of the circuitry shown in FIG. 7;

FIG. 8 depicts an embodiment of the invention wherein stretchablecircuitry is applied to a balloon catheter, in which the ballooncatheter is inflated;

FIG. 9A shows a side view of a balloon with a PDMS layer wrapped aroundthe surface of the balloon;

FIG. 9B is a cross-sectional view which shows the catheter, the surfaceof the balloon, and the thin PDMS layer applied to the balloon;

FIGS. 10A, B, and C depict a process for applying stretchable circuitryto the surface of a catheter balloon;

FIG. 10D is an embodiment of a pressure sensor utilized with embodimentsof the invention;

FIG. 10E is a cross-sectional view of a tri-lumen catheter according toembodiments of the invention;

FIG. 10F schematically depicts a multiplexor according to an embodimentof the present invention;

FIG. 11 is a schematic depiction of an embodiment of the inventioninvolving a neural prosthesis;

FIG. 12 is a circuit diagram for an embodiment of the invention;

FIG. 13 depicts a process for operating an array of electronic devicesaccording to an embodiment of the present invention;

FIG. 14 depicts an embodiment of the invention involving a neuralprosthesis;

FIG. 15 depicts an embodiment of the invention having a reservoir forholding and delivering a therapeutic agent, along with valves controlledby the circuitry to deliver said therapeutic agent;

FIG. 16 depicts a process for assembling curvilinear circuitry accordingto an embodiment of the invention;

FIGS. 16A and B depicts the process for applying a curvilinear array ofcircuitry to an endoscopic device according to an embodiment of theinvention;

FIG. 17 depicts an embodiment of an endoscopic device according to thepresent invention; and

FIG. 18 depicts a tissue screening device according to an embodiment ofthe invention.

DETAILED DESCRIPTION OF THE INVENTION

Detailed embodiments of the present invention are disclosed herein;however, it is to be understood that the disclosed embodiments aremerely exemplary of the invention, which can be embodied in variousforms. Therefore, specific structural and functional details disclosedherein are not to be interpreted as limiting but merely as a basis forthe claims and as a representative basis for teaching one skilled in theart to variously employ the present invention in virtually anyappropriately detailed structure. Further, the terms and phrases usedherein are not intended to be limiting but rather to provide anunderstandable description of the invention.

The terms “a” or “an,” as used herein, are defined as one or more thanone. The term “another,” as used herein, is defined as at least a secondor more. The terms “including” and/or “having” as used herein, aredefined as comprising (i.e., open transition). The term “coupled” or“operatively coupled,” as used herein, is defined as connected, althoughnot necessarily directly and not necessarily mechanically or physically.“Electronic communication” is the state of being able to convey orotherwise transmit data either through a physical connection, wirelessconnection, or combinations thereof

As described herein, the present invention comprises devices, systems,and methods utilizing flexible and/or stretchable electronic circuits onflexible, expandable, or inflatable surfaces. With reference to thepresent invention, the term “stretchable”, and roots and derivationsthereof, when used to modify circuitry or components thereof describescircuitry and/or components thereof having soft or elastic propertiescapable of being made longer or wider without tearing or breaking, andit is also meant to encompass circuitry having components (whether ornot the components themselves are individually stretchable as statedabove) that are configured in such a way so as to accommodate astretchable, inflatable, or expandable surface and remain functionalwhen applied to a stretchable, inflatable, or otherwise expandablesurface that is stretched, inflated, or otherwise expanded respectively.The term “expandable”, and roots and derivations thereof, when used tomodify circuitry or components thereof is also meant to have the meaningascribed above. Thus, “stretch” and “expand”, and all derivationsthereof, may be used interchangeably when referring to the presentinvention. The term “flexible”, and roots and derivations thereof, whenused to modify circuitry or components thereof describes circuitryand/or components thereof capable of bending without breaking, and it isalso meant to encompass circuitry having components (whether or not thecomponents themselves are individually flexible as stated above) thatare configured in such a way so as to accommodate a flexible surface andremain functional when applied to a flexible surface that is flexed orotherwise bent. In embodiments, at the low end of ‘stretchable’, thismay translate into material stains greater than 0.5% without fracturing,and at the high end to structures that may stretch 100,000% without adegradation of electrical performance. “Bendable” and roots andderivations thereof, when used to modify circuitry or components thereofdescribes circuitry and/or components thereof able to be shaped (atleast in part) into a curve or angle, and may sometimes be usedsynonymously herein with “flexible”.

FIG. 1 is a schematic depiction of embodiments of the invention. Furtherdescription of each of the components of FIG. 1 will be includedthroughout the specification. Circuitry 1000S is applied, secured, orotherwise affixed to substrate 200. In embodiments, substrate 200 isstretchable and or expandable as described herein. As such the substrate200 can be made of a plastic material or can be made of an elastomericmaterial, or combinations thereof. Note that the term “plastic” mayrefer to any synthetic or naturally occurring material or combination ofmaterials that can be molded or shaped, generally when heated, andhardened into a desired shape. The term “elastomer” may refer anaturally occurring material or a synthetic material, and also to apolymeric material which can be stretched or deformed and return to itsoriginal shape without substantial permanent deformation. Suchelastomers may withstand substantial elastic deformations. Examples ofelastomers used in substrate material include polymeric organosiliconcompounds (commonly referred to as “silicones”) includingPolydimethylsiloxane (PDMS).

Other materials suitable for the substrate include polyimide;photopatternable silicone; SU8 polymer; PDS polydustrene; parylene andits derivatives and copolymers (parylene-N); ultrahigh molecular weightpolyethylene; poly ether ether ketones (PEEK); polyurethanes (PTGElasthane®, Dow Pellethane®); polylactic acid; polyglycolic acid;polymer composites (PTG Purisil Al®, PTG Bionate®, PTG Carbosil);silicones/siloxanes (RTV 615®, Sylgard 1840); polytetrafluoroethylene(PTFE, Teflon 0); polyamic acid; polymethyl acrylate; stainless steel;titanium and its alloys; platinum and its alloys; and gold. Inembodiments, the substrate is made of a stretchable or flexiblebiocompatible material having properties which may allow for certaindevices to be left in the body 2000 for a period of time without havingto be retrieved.

Some of the materials mentioned above, specifically parylene and itsderivatives and copolymers (parylene-N); ultrahigh molecular weightpolyethylene; poly ether ether ketones (PEEK); polyurethanes (PTGElasthane®, Dow Pellethane®); polylactic acid; polyglycolic acid;polymer composites (PTG Purisil Al®, PTG Bionate®, PTG Carbosil);silicones/siloxanes (RTV 615®, Sylgard 184®); polytetrafluoroethylene(PTFE, Teflon 0); polyamic acid; polymethyl acrylate; stainless steel;titanium and its alloys; platinum and its alloys; and gold, arebiocompatible. Coatings for the substrate to increase itsbiocompatibility may include, PTFE, polylactic acid, polyglycolic acid,and poly(lactic-co-glycolic acid).

The materials disclosed for substrate 200 herein may be understood toapply to any of the embodiments disclosed herein that require substrate.It should also be noted that materials can be chosen based on theirproperties which include degree of stiffness, degree of flexibility,degree of elasticity, or such properties related to the material'selastic moduli including Young's modulus, tensile modulus, bulk modulus,shear modulus, etc., and or their biodegradability.

The substrate 200 can be one of any possible number of shapes orconfigurations. In embodiments, the substrate 200 is substantially flatand in some embodiments configured to be a sheet or strip. Yet it shouldbe noted that such flat configurations of substrate 200 can be anynumber of geometric shapes. Other embodiments of flat substrates will bedescribed below including substrates having a tape-like or sheetconfiguration. Flexible and/or stretchable substrate 200 having a sheetor otherwise substantially flat configuration may be configured suchthat substrate 200 can be folded, furled, bunched, wrapped or otherwisecontained. In embodiments, a substrate 200 configured as such can befolded, furled, bunched, collapsed (such as in an umbrella-likeconfiguration), wrapped, or otherwise contained during delivery throughnarrow passageways in the subject's body 2000 and then deployed into anunfolded, unfurled, etc. state once in position for deployment. As anon-limiting example, a furled substrate 200 carrying circuitry 100Scomprising sensing device 1100 could be delivered via a catheter, thenunfurled at such point when it is desired for the sensing device tocontact the tissue of interest, such as the surface of the heart, or theinner surface of a lumen such as the pulmonary vein. In embodiments,substrates 200 may also be formed into concave and convex shapes, suchas lenses. Such convex and concave substrates can be made of materialsuitable for contact with the eye, such as a contact lens orimplantation into the eye, such a retinal or corneal implant.

Substrate 200 may also be three-dimensional. The three-dimensionalsubstrate 200 can be any number of shapes. Such three-dimensionalsubstrates may be a solid or substantially solid. In embodiments, thethree-dimensional substrate may be pliable, flexible and stretchablewhile still comprising homogeneous or substantially homogenous materialthroughout its form, such as a foam or a flexible/stretchable polymericsphere, ovoid, cylinder, disc, or other three-dimensional object. Inembodiments, the three-dimensional substrate 200 may be made fromseveral materials. In the presently preferred embodiment for thethree-dimensional substrate 200, the substrate is an inflatable body(also referred to herein as an elastomeric vessel). Inflatable bodies ofthis type may be stretchable, such as a balloon or the like; however, inother embodiments, the inflatable body inflates without stretching. Inembodiments, inflation can be achieved via a gas or liquid. In certainembodiments, inflation with a viscous fluid is preferable, but it shouldbe clear that a variety of gases, fluids or gels may be employed forsuch inflation. Embodiments comprising balloon-like and disc-likeinflatable substrates will be discussed in further detail below. Thesystems to achieve inflation discussed in connection with thoseembodiments apply to all inflatable embodiments of substrate herein.

In embodiments where the substrate 200 is stretchable, circuitry 1000Sis configured in the applicable manners described herein to bestretchable and/or to accommodate such stretching of the substrate 200.Similarly, in embodiments where the substrate 200 is flexible, but notnecessarily stretchable, circuitry 1000S is configured in the applicablemanners described herein to be flexible and/or accommodate such flexingof the substrate 200. Circuitry 1000S can be applied and/or configuredusing applicable techniques described below, including those describedin connection with exemplary embodiments.

As mentioned above, the present invention may employ one or more of aplurality of flexible and/or stretchable electronics technologies in theimplementation thereof. Traditionally, electronics have been fabricatedon rigid structures, such as on integrated circuits, hybrid integratedcircuits, flexible printed circuit boards, and on printed circuitboards. Integrated circuits, also referred to as ICs, microcircuits,microchips, silicon chips, or simple chips, have been traditionallyfabricated on a thin substrate of semiconductor material, and have beenconstrained to rigid substrates mainly due to the high temperaturesrequired in the step of inorganic semiconductor deposition. Hybridintegrated circuits and printed circuit boards have been the main methodfor integrating multiple ICs together, such as through mounting the ICsonto a ceramic, epoxy resin, or other rigid non-conducting surface.These interconnecting surfaces have traditionally been rigid in order toensure that the electrical interconnection methods, such as solderjoints to the board and metal traces across the boards, do not break orfracture when flexed. In addition, the ICs themselves may fracture ifflexed. Thus, the field of electronics has been largely constrained torigid electronics structures, which then tend to constrain electronicsapplications that may require flexibility and or stretchabilitynecessary for the embodiments disclosed herein. For example,high-quality sensing can be achieved by enabling the electronic devices,such as sensor device, into intimate or direct contact with tissues ofinterest. The rigidity of devices described above has prevented suchdirect contact. Embodiments described below achieve such direct contact(in some cases described as “conformal contact”).

Advancements in flexible and bendable electronics technologies haveemerged that enable flexible electronics applications, such as withorganic and inorganic semiconductors on flexible plastic substrates, andother technologies described herein. Further, stretchable electronicstechnologies have emerged that enable applications that require theelectronics to be stretchable, such as through the use of mounting ICson flexible substrates and interconnected through some method ofstretchable electrical interconnect, and other technologies as describedherein. The present invention may utilize one or more of these flexible,bendable, stretchable, and like technologies, in applications thatrequire the electronics to operate in configurations that may not be, orremain, rigid and planar, such as applications that require electronicsto flex, bend, expand, stretch and the like.

In embodiments, the circuitry of the invention may be made in part or infull by utilizing the techniques and processes described below. Notethat the below description of the various ways to achieve stretchableand/or flexible electronics is not meant to be limiting, and encompassessuitable variants and or modifications within the ambit of one skilledin the art. As such, this application will refer to the following UnitedStates Patents and Patent Applications, each of which is incorporated byreference herein in its entirety: U.S. Pat. No. 7,557,367 entitled“Stretchable Semiconductor Elements and Stretchable ElectricalCircuits”, issued Jul. 7, 2009 (the “'367 patent”); U.S. Pat. No.7,521,292 entitled “Stretchable Form of Single Crystal Silicon for HighPerformance Electronics on Rubber Substrates”, issued Apr. 29, 2009 (the“'292 patent”); United States Published Patent Application No.20080157235 entitled “Controlled Buckling Structures in SemiconductorInterconnects and Nan membranes for Stretchable Electronics”, filed Sep.6, 2007 (the “'235 application”); U.S. patent application having Ser.No. 12/398,811 entitled “Stretchable and Foldable Electronics”, filedMar. 5, 2009 (the “'811 application”); United States Published PatentApplication No. 20040192082 entitled “Stretchable and ElasticInterconnects” filed March 28, 2003 (the “'082 application”); UnitedStates Published Patent Application No. 20070134849 entitled “Method ForEmbedding Dies”, filed Nov. 21, 2006 (the “'849 application”); UnitedStates Published Patent Application No. 20080064125 entitled “ExtendableConnector and Network, filed Sep. 12, 2007 (the “'125 application”);U.S. Provisional Patent Application having Ser. No. 61/240,262 (the“'262 application”) “Stretchable Electronics”, filed Sep. 7, 2009; U.S.patent application having Ser. No. 12/616,922 entitled “ExtremelyStretchable Electronics”, filed Nov. 12, 2009 (the “'922 application”);U.S. Provisional Patent Application having Ser. No. 61/120,904 entitled“Transfer Printing”, filed Dec. 9, 2008 (the “'904 application”); U.S.Published Patent Application No. 20060286488 entitled “Methods andDevices for Fabricating Three-Dimensional Nanoscale Structures”, filedDec. 1, 2004; U.S. Pat. No. 7,195,733 entitled “Composite PatterningDevices for Soft Lithography” issued Mar. 27, 2007; United StatesPublished Patent Application No. 20090199960 entitled “Pattern TransferPrinting by Kinetic Control of Adhesion to an Elastomeric Stamp” filedJun. 9, 2006; United States Published Patent Application. No.20070032089 entitled “Printable Semiconductor Structures and RelatedMethods of Making and Assembling” filed Jun. 1, 2006; United StatesPublished Patent Application No. 20080108171 entitled “ReleaseStrategies for Making Transferable Semiconductor Structures, Devices andDevice Components” filed Sep. 20, 2007; and United States PublishedPatent Application No. 20080055581 entitled “Devices and Methods forPattern Generation by Ink Lithography”, filed Feb. 16, 2007.

“Electronic device” is used broadly herein to encompass an integratedcircuit(s) having a wide range of functionality. In embodiments, theelectronic devices may be devices laid out in a device islandarrangement, as described herein including in connection to exemplaryembodiments. The devices can be, or their functionality can include,integrated circuits, processors, controllers, microprocessors, diodes,capacitors, power storage elements, antennae, ASICs, sensors,amplifiers, A/D and D/A converters, associated differential amplifiers,buffers, microprocessors, optical collectors, transducer includingelectro-mechanical transducers, piezo-electric actuators, light emittingelectronics which include LEDs, logic, memory, clock, and transistorsincluding active matrix switching transistors, and combinations thereof. The purpose and advantage of using standard ICs (in embodiments, CMOS,on single crystal silicon) is to have and use high quality, highperformance, and high functioning circuit components that are alsoalready commonly mass-produced with well known processes, and whichprovide a range of functionality and generation of data far superior tothat produced by a passive means. Components within electronic devicesor devices are described herein, and include those components describedabove. A component can be one or more of any of the electronic devicesdescribed above and/or may include a photodiode, LED, TUFT, electrode,semiconductor, other light-collecting/detecting components, transistor,contact pad capable of contacting a device component, thin-film devices,circuit elements, control elements, microprocessors, interconnects,contact pads, capacitors, resistors, inductors, memory element, powerstorage element, antenna, logic element, buffer and/or other passive oractive components. A device component may be connected to one or morecontact pads as known in the art, such as metal evaporation, wirebonding, application of solids or conductive pastes, and the like.

Components incapable of controlling current by means of anotherelectrical signal are called passive devices. Resistors, capacitors,inductors, transformers, and diodes are all considered passive devices

For purposes of the invention, an active device is any type of circuitcomponent with the ability to electrically control electron flow. Activedevices include, but are not limited to, vacuum tubes, transistors,amplifiers, logic gates, integrated circuits, silicon-controlledrectifiers (SCRs), and triode for alternating current (TRIACs).

“Ultrathin” refers to devices of thin geometries that exhibitflexibility.

“Functional layer” refers to a device layer that imparts somefunctionality to the device. For example, the functional layer may be athin film, such as a semiconductor layer. Alternatively, the functionallayer may comprise multiple layers, such as multiple semiconductorlayers separated by support layers. The functional layer may comprise aplurality of patterned elements, such as interconnects running betweendevice-receiving pads.

Semiconductor materials which may be used to make circuits may includeamorphous silicon, polycrystalline silicon, single crystal silicon,conductive oxides, carbon annotates and organic materials.

In some embodiments of the invention, semiconductors are printed ontoflexible plastic substrates, creating bendable macro-electronic,micro-electronic, and/or nano-electronic devices. Such bendable thinfilm electronics devices on plastic may exhibit field effect performancesimilar to or exceeding that of thin film electronics devices fabricatedby conventional high temperature processing methods. In addition, theseflexible semiconductor on plastic structures may provide bendableelectronic devices compatible with efficient high throughput processingon large areas of flexible substrates at lower temperatures, such asroom temperature processing on plastic substrates. This technology mayprovide dry transfer contact printing techniques that are capable ofassembling bendable thin film electronics devices by depositing a rangeof high quality semiconductors, including single crystal Si ribbons,GaAs, INP wires, and carbon nano-tubes onto plastic substrates. Thishigh performance printed circuitry on flexible substrates enables anelectronics structure that has wide ranging applications. The '367patent and associated disclosure illustrates an example set of steps forfabricating a bendable thin film electronics device in this manner. (SeeFIG. 26A of the '367 patent for Example).

In addition to being able to fabricate semiconductor structures onplastic, it has been demonstrated that metal-semiconductor electronicsdevices may be formed with printable wire arrays, such as GaAsmicro-wires, on the plastic substrate. Similarly, other high qualitysemiconductor materials have been shown to transfer onto plasticsubstrates, including Si nano-wires, micro-ribbons, platelets, and thelike. In addition, transfer printing techniques using elastomeric stampsmay be employed. The '367 patent provides an example illustration of themajor steps for fabricating, on flexible plastic substrates, electronicsdevices that use arrays of single wires (in this instance GaAs wires)with epitaxial channel layers, and integrated holmic contacts. (See FIG.41 of the '367 patent). In an example, a semi-insulating GaAs wafer mayprovide the source material for generating the micro-wires. Each wiremay have multiple ohmic stripes separated by a gap that defines thechannel length of the resultant electronic device. Contacting a flat,elastomeric stamp of PDMS to the wires forms a van der Waals bond. Thisinteraction enables removal of all the wires from the wafer to thesurface of the PDMS when the stamp is peeled back. The PDMS stamp withthe wires is then placed against an uncured plastic sheet. After curing,peeling off the PDMS stamp leaves the wires with exposed ohmic stripesembedded on the surface of the plastic substrate. Further processing onthe plastic substrate may define electrodes that connect the ohmicstripes to form the source, drain, and gate electrodes of theelectronics devices. The resultant arrays are mechanically flexible dueto the bendability of the plastic substrate and the wires.

In embodiments, and in general, stretchable electronics may incorporateelectrodes, such as connected to a multiplexing chip and dataacquisition system. For example, such an electrode system may beintegrated into a medical application, such as in a catheter forneurological or cardiac monitoring and stimulation. In an example, anelectrode may be fabricated, designed, transferred, and encapsulated. Inan embodiment, the fabrication may utilize and/or include an SI wafer;spin coating an adhesion layer (e.g. an HMDS adhesion layer); spincoating (e.g. PMMA) patterned by shadow mask, such as in oxygen RIE;spin coating Polyimide; depositing PECVD SiO2; spin 1813 Resist,photolithography patterning; metal evaporation (e.g. Ti, Pt, Au, and thelike, or combination of the aforementioned); gold etchant, liftoff inhot acetone; spin Polyimide; PECVD SiO2; spin 1813 Resist,photolithography patterning; RIE etch, and the like. In this embodiment,the fabrication step may be complete with the electrodes on the Siwafer. In embodiments, the Si wafer may then be bathed in a hot acetonebath, such as at 100C for approximately one hour to release adhesionlayer while PI posts keep electrode adhered to the surface of the Siwafer. In embodiments, electrodes may be designed in a plurality ofshapes and distributed in a plurality of distribution patterns.Electrodes may be interconnected to electronics, multiplexingelectronics, interface electronics, a communications facility, interfaceconnections, and the like including any of the facilities/elementsdescribed on connection with FIG. 1 and/or the exemplary embodimentsherein. In embodiments, the electrodes may be transferred from the Siwafer to a transfer stamp, such as a PDMS stamp, where the material ofthe transfer stamp may be fully cured, partially cured, and the like.For example, a partially cured PDMS sheet may be ˜350 nm, where the PDMSwas spun on at 300 rpm for 60 s, cured 65 C. for 25 min, and used tolift electrodes off of the PDMS sheet. In addition, the electrodes maybe encapsulated, such as wherein the electrodes are sandwiched between asupporting PDMS layer and second PDMS layer while at least one of thePDMS layers is partially cured.

In embodiments, stretchable electronics configurations may incorporateflex PCB design elements, such as flex print, chip flip configurations(such as bonded onto the PCB), and the like, for connections toelectrodes and/or devices, and for connections to interface electronics,such as to a data acquisition system (DAQ). For example, a flex PCB maybe joined to electrodes by an anisotropic conductive film (ACF)connection, solder joints may connect flex PCB to the data acquisitionsystem via conductive wires, and the like. In embodiments, theelectrodes may be connected onto a surface by employing apartially-cured elastomer (e.g. PDMS) as an adhesive.

In embodiments, stretchable electronics may be formed into sheets ofstretchable electronics, such as to monitor neural signal activity viastretchable electrode systems as described below. In embodiments,stretchable sheets may be thin, such as approximately 100 um.Optionally, amplification and multiplexing may be implemented withoutsubstantially heating the contact area, such as with micro-fluidiccooling.

In embodiments, a sheet having arrays of electronic devices comprisingelectrodes may be cut into different shapes and remain functional, suchas through communicating electrode islands which determine the shape ofthe electrode sheet. Electrodes are laid out in a device islandarrangement (as described herein) and may contain active circuitrydesigned to communicate with each other via inter-island stretchableinterconnects so that processing facility (described herein) in thecircuitry can determine in real-time the identity and location of othersuch islands. In this way, if one island becomes defective, the islandscan still send out coordinated, multiplexed data from the remainingarray. Such functionality allows for such arrays to be cut and shapedbased on the size constraints of the application. A sheet, and thuscircuitry, may be cut to side and the circuitry will poll remainingelectrodes and/or devices to determine which are left and will modifythe calibration accordingly. An example of a stretchable electronicssheet containing this functionality, may include electrode geometry,such as a 20×20 array of platinum electrodes on lmm pitch for a totalarea of 20×20 mm²; an electrode impedance, such as 5 kohm at lkhz(adjustable); a configuration in a flexible sheet, such as with a 50 μmtotal thickness, and polyimide encapsulated; a sampling rate, such as 2kHz per channel; a voltage dynamic range, such as +/−6 mV; a dc voltageoffset range, such as −2.5 to 5 V, with dc rejection; a voltage noise,such as 0.002 mV, a maximum signal-to-noise ratio, such as 3000; aleakage current, such as 0.3 μA typical, 10 μA maximum, as meets IECstandards, and the like; an operating voltage of 5 V; an operating powerper channel, such as less than 2 mW (adjustable); a number of interfacewires, such as for power, ground, low impedance ground, data lines, andthe like; a voltage gain, such as 150; a mechanical bend radius, such as1 mm; a local heating capability, such as heating local tissue by up to1° C.; biocompatibility duration, such as 2 weeks; active electronics,such as a differential amplifier, a multiplexer (e.g. 1000 transistorsper channel); a data acquisition system, such as with a 16 bit A/Dconverter with a 500 kHz sampling rate, less than 2 μV noise, data loginand real-time screen display; safety compliance, such as to IEC10601;and the like.

In embodiments of the invention, mechanical flexibility may represent animportant characteristic of devices, such as on plastic substrates, formany applications. Micro/nano-wires with integrated ohmic contactsprovide a unique type of material for high performance devices that canbe built directly on a wide range of device substrates. Alternatively,other materials may be used to connect electrical components together,such as connecting electrically and/or mechanically by thin polymerbridges with or without metal interconnects lines.

In embodiments, an encapsulation layer may be utilized. An encapsulatinglayer may refer to coating of the device, or a portion of the device. Inembodiments, the encapsulation layer may have a modulus that isinhomogeneous and/or that spatially varies. Encapsulation layers mayprovide mechanical protection, device isolation, and the like. Theselayers may have a significant benefit to stretchable electronics. Forexample, low modulus PDMS structures may increase the range ofstretchability significantly (described at length in the '811application). The encapsulation layer may also be used as a passivationlater on top of devices for the protection or electrical isolation. Inembodiments, the use of low modulus strain isolation layers may allowintegration of high performance electronics. The devices may have anencapsulation layer to provide mechanical protection and protectionagainst the environment. The use of encapsulation layers may have asignificant impact at high strain. Encapsulants with low moduli mayprovide the greatest flexibility and therefore the greatest levels ofstretchability. As referred to in the '811 application, low modulusformulations of PDMS may increase the range of stretchability at leastfrom 60%. Encapsulation layers may also relieve strains and stresses onthe electronic device, such as on a functional layer of the device thatis vulnerable to strain induced failure. In embodiments, a layering ofmaterials with different moduli may be used. In embodiments, theselayers may be a polymer, an elastomer, and the like. In embodiments, anencapsulation may serve to create a biocompatible interface between animplanted stretchable electronic system, such as Silk encapsulation ofelectronic devices in contact with tissue.

Returning to flexible and stretchable electronics technologies that maybe utilized in the present invention, it has been shown that buckled andwavy ribbons of semiconductor, such as GaAs or Silicon, may befabricated as part of electronics on elastomeric substrates.Semiconductor ribbons, such as with thicknesses in the submicron rangeand well-defined, ‘wavy’ and/or ‘buckled’ geometries have beendemonstrated. The resulting structures, on the surface of, or embeddedin, the elastomeric substrate, have been shown to exhibit reversiblestretchability and compressibility to strains greater than 10%. Byintegrating ohmic contacts on these structured GaAs ribbons,high-performance stretchable electronic devices may be achieved. The'292 patent illustrates steps for fabricating stretchable GaAs ribbonson an elastomeric substrate made of PDMS, where the ribbons aregenerated from a high-quality bulk wafer of GaAs with multiple epitaxiallayers (See FIG. 22). The wafer with released GaAs ribbons is contactedto the surface of a pre-stretched PDMS, with the ribbons aligned alongthe direction of stretching. Peeling the PDMS from the mother wafertransfers all the ribbons to the surface of the PDMS. Relaxing theprestrain in the PDMS leads to the formation of large scale buckles/wavystructures along the ribbons. The geometry of the ribbons may depend onthe prestrain applied to the stamp, the interaction between the PDMS andribbons, and the flexural rigidity of the ribbons, and the like. Inembodiments, buckles and waves may be included in a single ribbon alongits length, due for example, to thickness variations associated withdevice structures. In practical applications, it might be useful toencapsulate the ribbons and devices in a way that maintains theirstretchability. The semiconductor ribbons on an elastomeric substratemay be used to fabricate high-performance electronic devices, buckledand wavy ribbons of semiconductor multilayer stacks and devicesexhibiting significant compressibility/stretchability. In embodiments,the present invention may utilize a fabrication process for producing anarray of devices utilizing semiconductor ribbons, such as an array ofCMOS inverters with stretchable, wavy interconnects. Also, a strategy oftop layer encapsulation may be used to isolate circuitry from strain,thereby avoiding cracking.

In embodiments, a neutral mechanical plane (NMP) in a multilayer stackmay define the position where the strains are zero. For instance, thedifferent layers may include a support layer, a functional layer, aneutral mechanical surface adjusting layer, an encapsulation layer witha resultant neutral mechanical surface such as coincident with thefunctional layer, and the like. In embodiments, the functional layer mayinclude flexible or elastic device regions and rigid island regions. Inembodiments, an NMP may be realized in any application of thestretchable electronics as utilized in the present invention.

In embodiments, semiconductor ribbons (also, micro-ribbons,nano-ribbons, and the like) may be used to implement integratedcircuitry, electrical interconnectivity between electrical/electroniccomponents, and even for mechanical support as a part of an electrical/electronic system. As such, semiconductor ribbons may be utilized in agreat variety of ways in the configuration /fabrication of flexible andstretchable electronics, such as being used for the electronics orinterconnection portion of an assembly leading to a flexible and/orstretchable electronics, as an interconnected array of ribbons forming aflexible and/or stretchable electronics on a flexible substrate, and thelike. For example, nano-ribbons may be used to form a flexible array ofelectronics on a plastic substrate. The array may represent an array ofelectrode-electronics cells, where the nano-ribbons are pre-fabricated,and then laid down and interconnected through metallization andencapsulation layers. Note that the final structure of thisconfiguration may be similar to electronic device arrays as fabricateddirectly on the plastic, as described herein, but with the higherelectronics integration density enabled with the semiconductor ribbons.In addition, this configuration may include encapsulation layers andfabrication steps which may isolate the structure from a wetenvironment. This example is not meant to limit the use of semiconductorribbons in any way, as they may be used in a great variety ofapplications associated with flexibility and stretchability. Forexample, the cells of this array may be instead connected by wires, bentinterconnections, be mounted on an elastomeric substrate, and the like,in order to improve the flexibility and/or stretchability of thecircuitry.

Wavy semiconductor interconnects is only one form of a broader class offlexible and stretchable interconnects that may (in some cases) bereferred to as ‘bent’ interconnects, where the material may besemiconductor, metal, or other conductive material, formed in ribbons,bands, wire, traces, and the like. A bent configuration may refer to astructure having a curved shape resulting from the application of aforce, such as having one or more folded regions. These bentinterconnections may be formed in a variety of ways, and in embodiments,where the interconnect material is placed on an elastomeric substratethat has been pre-strained, and the bend form created when the strain isreleased. In embodiments, the pre-strain may be pre-stretched orpre-compressed, provided in one, two, or three axes, providedhomogeneously or heterogeneously, and the like. The wavy patterns may beformed along pre-strained wavy patterns, may form as ‘pop-up’ bridges,may be used with other electrical components mounted on the elastomer,or transfer printed to another structure. Alternately, instead ofgenerating a ‘pop-up’ or buckled components via force or strainapplication to an elastomeric substrate, a stretchable and bendableinterconnect may be made by application of a component material to areceiving surface. Bent configurations may be constructed frommicro-wires, such as transferred onto a substrate, or by fabricatingwavy interconnect patterns either in conjunction with electronicscomponents, such as on an elastomeric substrate.

Semiconductor nanoribbons, as described herein, may utilize the methodof forming wavy ‘bent’ interconnections through the use of forming thebent interconnection on a pre-strained elastomeric substrate, and thistechnique may be applied to a plurality of different materials. Anothergeneral class of wavy interconnects may utilize controlled buckling ofthe interconnection material. In this case, a bonding material may beapplied in a selected pattern so that there are bonded regions that willremain in physical contact with the substrate (after deformation) andother regions that will not. The pre-strained substrate is removed fromthe wafer substrate, and upon relaxation of the substrate, the unboundedinterconnects buckle (pop-up′) in the unbonded (or weakly bonded)regions. Accordingly, buckled interconnects impart stretchability to thestructure without breaking electrical contact between components,thereby providing flexibility and/or stretchability. FIG. 2 shows asimplified diagram showing a buckled interconnection 204S between twocomponents 202S and 208S.

In embodiments, any, all, or combinations of each of the interconnectionschemes described herein may be applied to make an electronics supportstructure more flexible or bendable, such as applying bent interconnectsto a flexible substrate, such as plastic or elastomeric substrates.However, these bent interconnect structures may provide for asubstantially more expandable or stretchable configuration in anothergeneral class of stretchable electronic structures, where rigidsemiconductor islands are mounted on an elastomeric substrate andinterconnected with one of the plurality of bent interconnecttechnologies. This technology is presented here, and also in the '262application, which has been incorporated by reference in its entirety.This configuration also uses the neutral mechanical plane designs, asdescribed herein, to reduce the strain on rigid components encapsulatedwithin the system. These component devices may be thinned to thethickness corresponding to the desired application or they may beincorporated exactly as they are obtained. Devices may then beinterconnected electronically and encapsulated to protect them from theenvironment and enhance flexibility and stretchability.

In an embodiment, the first step in a process to create stretchable andflexible electronics as described herein involves obtaining requiredelectronic devices and components and conductive materials for thefunctional layer. The electronics are then thinned (if necessary) byusing a back grinding process. Many processes are available that canreliably take wafers down to 50 microns. Dicing chips via plasma etchingbefore the grinding process allows further reduction in thickness andcan deliver chips down to 20 microns in thickness. For thinning,typically a specialized tape is placed over the processed part of thechip. The bottom of the chip is then thinned using both mechanicaland/or chemical means. After thinning, the chips may be transferred to areceiving substrate, wherein the receiving substrate may be a flatsurface on which stretchable interconnects can be fabricated. FIG. 3illustrates an example process, which begins by creating a flexiblesubstrate 302S on the carrier 308S coated with a sacrificial layer 304S(FIG. 3A), placing devices 310S on the flexible substrate (FIG. 3B), andperforming a planarization step in order to make the top surface of thereceiving substrate the same height as that of the die surface (FIG.3C). The interconnect fabrication process follows. The devices 310Sdeposited on the receiving substrate are interconnected 312S which joinbond pads from one device to another (FIG. 3D). In embodiments, theseinterconnects 312S may vary from 10 microns to 10 centimeters. Apolymeric encapsulating layer 314S may then be used to coat the entirearray of interconnected electronic devices and components (FIG. 2E). Theinterconnected electronic devices are then released from the substrateby etching away sacrificial materials with a solvent. The devices arethen ready to undergo stretch processing. They are transferred from therigid carrier substrate to an elastomeric substrate such as PDMS. Justbefore the transfer to the new substrate, the arrays are pre-treatedsuch that the device/component islands preferentially adhere to thesurface leaving the encapsulated interconnects free to be displacedperpendicular to the receiving substrate.

In embodiments, the interconnect system is a straight metal lineconnecting two or more bond pads. In this case the electronic array istransferred to a pre-strained elastomeric substrate. Upon relaxation ofthis substrate the interconnects will be displaced perpendicular to thesubstrate, thus producing outward buckling. This buckling enablesstretching of the system.

In another embodiment, the interconnects are a serpentine pattern ofconductive metal. These types of interconnected arrays need not bedeposited on a pre-strained elastomeric substrate. The stretchability ofthe system is enabled by the winding shape of the interconnects.

Stretchable/flexible circuits may be formed on paper, plastic,elastomeric, or other materials with the aid of techniques including butnot limited to conventional photolithographic techniques, sputtering,chemical vapor deposition, ink jet printing, or organic materialdeposition combined with patterning techniques. Semiconductor materialswhich may be used to make circuits may include amorphous silicon,polycrystalline silicon, single-crystal silicon, conductive oxides,carbon nanotubes and organic materials. In embodiments, theinterconnects may be formed of electrically conducting film, stripe,pattern, and the like, such as on an elastomer or plastic material,where the film may be made to buckle, deform, stretch, and the like, asdescribed herein. In embodiments, the interconnect may be made of aplurality of films, such as on or embedded in the flexible and/or astretchable substrate or plastic.

In embodiments, the interconnection of device islands 402S may utilizean extremely stretchable interconnect 404S, such as shown in FIG. 4, andsuch as the various configurations disclosed in the '922 application.The geometry and the dimension of the interconnects 404S is what makesthem extremely compliant. Each interconnect 404S is patterned and etchedso that its structural form has width and thickness dimensions that maybe of comparable size (such as their ratio or inverse ratio notexceeding about a factor of 10); and may be preferably equal in size. Inembodiments, the interconnect may be formed in a boustrophedonic stylesuch that it effectively comprises long bars 408S and short bars 410S.This unique geometry minimizes the stresses that are produced in theinterconnect when subsequently stretched because it has the effectiveform of a wire, and behaves very differently than interconnect formfactors having one dimension greatly exceeding the other two (forexample plates). Plate type structures primarily relieve stress onlyabout a single axis via buckling, and withstand only a slight amount ofshear stress before cracking. This invention may relieve stress aboutall three axes, including shears and any other stress. In addition,because the interconnect may be formed out of rigid materials, afterbeing stretched it may have a restorative force which helps prevent itswire-like form from getting tangled or knotted when re-compressing tothe unstretched state. Another advantage of the boustrophedonic geometryis that it minimizes the initial separation distance between theislands. In embodiments, the interconnects may be formed eithermonolithically (i.e., out of the same semiconductor material as thedevice islands) or may be formed out of another material.

In another embodiment the elastomeric substrate may comprise two layersseparated by a height 512S, such as shown in FIG. 5. The top “contact”layer contacts the device island 502S, where the device islands 502S areinterconnected 504S with one of the interconnection schemes describedherein. In addition, the bottom layer may be a “wavy” layer containingripples 514S or square waves molded into the substrate 508S duringelastomer fabrication. These waves enable additional stretching, whoseextent may depend on the amplitude 510S and wavelength of the wavespattern-molded in the elastomer.

In embodiments, the device island may be any prefabricated integratedcircuit (IC), where the IC may be mounted on, inside, between, and thelike, a flexible and/or stretchable substrate. For example, anadditional elastomeric layer may be added above the structure as shownin FIG. 5, such as to encapsulate the structure for protection,increased strength, increase flexibility, and the like. Electricalcontacts to embedded electrical components may be provided across theembedded layer, through the elastomeric layer(s) from a secondelectrical interconnection layer, and the like. For example, an IC maybe encapsulated in a flexible material where the interconnects are madeaccessible as described in the '849 application. (Se FIG. 1 of the '849application for example). In this example the embedded IC is fabricatedby first placing the IC onto a carrier, such as a rigid carrier, andwhere the IC may be a thinned IC (either thinned before the mounting onthe carrier, or thinned while on the carrier). A second step may involvea coating of the IC with some adhesive, elastomer, or other insulatingmaterial that can be flowed onto the IC. A third step may be to gainaccess to the electrical contacts of the IC, such as by laser drillingor other method known to the art. A fourth step may be to flowelectrical conductor into the openings, thus establishing a electricalaccess to the electrical connections of the IC. Finally, the IC thusencased may be freed from the carrier. Now the structure may be moreeasily embedded into a flexible substrate while maintaining electricalconnectivity. In embodiments, this structure may be a flexiblestructure, due to the thinness of the IC, the elastic character of thesurrounding structure, the elastic configuration of the extendedelectrical contacts, and the like.

It should be noted that many of the stretchable electronics techniquesutilize the process of transfer printing, for example, with a PDMSstamp. In embodiments, the present invention may include a method ofdynamically controlling the surface adhesion of a transfer printingstamp, such as described here, and disclosed in the '904 application.Transfer printing stamps have many uses, one of which is to pick up thinfilms of materials (“targets”) from one surface (“initial surface”) anddeposit them onto another surface (“final surface”). The pickup may beachieved by pressing the transfer printing stamp into contact with thetargets, applying some pressure to create Van der Waals bonds betweenthe stamp and the targets, peeling off the stamp with the targets, andthen placing the stamp with targets into contact with another surface,applying pressure, and peeling off the stamp without the targets so theyremain on the final surface. If the final surface has a higher bondingstrength with the targets than the transfer stamp, they will remain onthe final surface when the transfer stamp is peeled off. Alternately,the rate of peeling the transfer stamp can be adjusted to vary thetarget to stamp and target to final surface bonding force ratio. Thepresent invention describes a novel method of depositing the targets, bychanging the surface adhesion of the transfer stamp after the targetshave been picked up. This may be done while the stamp with targets is incontact with the final surface. In embodiments, the adhesion control canbe done by introducing micro-fluidic channels into the transfer stamp,so that water or other fluid can be pumped to the surface of the stampfrom within it, thereby changing the surface adhesion from sticky tonon-sticky.

In embodiments, the present invention may accomplish transfer printingby using a transfer printing stamp that has been formed withmicro-fluidic channels such that a fluid (liquid or gas) can be pumpedto the surface of the stamp to wet or chemically functionalize thesurface and therefore change the surface adhesion of the stamp surface.The transfer printing stamp may be made out of any material, includingbut not limited to poly-dimethyl-siloxane (PDMS) and derivativesthereof. In one non-limiting embodiment, the stamp is a piece of PDMSformed into a cuboid, which may have dimensions ranging from about 1micrometer to 1 meter. For this example, the cuboid is 1 cm×1 cm×0.5 cm(length, width, thickness). One 1 cm×1 cm surface of the cuboid isdesignated as the stamping face. By using a photolithography mask, or astencil mask, a pattern of vertical holes (channels) is etched from thestamping face through to the opposing face of the stamp. This may bedone with an oxygen reactive ion etch. These holes are the micro-fluidicchannels, and may be about 0.1-10 micrometers in diameter. They may bespaced apart by about 1-50 micrometers. Another piece of PDMS may beformed into a reservoir shape (eg. a 1 cm×1 cm×0.5 cm cuboid with asmaller cuboid (about 0.8 cm×0.8 cm×0.3 cm) cut out from one surface).This shape may be formed by pouring the PDMS into a mold, curing it, andremoving it from the mold. This additional piece of PDMS may then beplaced into contact with the first piece of PDMS and bonded (this may bedone via ultraviolet ozone exposure or oxygen plasma exposure of thePDMS prior to contacting the two pieces) such that the two pieces formthe shape shown in FIG. 6, step A. Then, one or more holes may bepunctured into the top of the reservoir so that a fluidic pipe can befitted for pumping water into the stamp. In another non-limitingembodiment, the stamp is constructed as described above, except that thefirst piece of PDMS is formed to have micro-fluidic channels by means ofmolding. PDMS molding is a well known art. First, a mold is created thatis the inverse of the desired shape. In this case, that is an array ofvertical posts on a base with four walls. This mold is then filled withPDMS by pouring in the PDMS, allowing it to cure (which may be atelevated temperature), and then removing the PDMS. In anothernon-limiting embodiment, the stamping surface is also patterned with anarray of shallow-etched surface channels. In embodiments, these channelsmay be about 100 -10000 nm wide, and 100-10000 nm etched-into the PDMS.They may form a linear array or a checkerboard grid. The purpose of thechannels is to help distribute a liquid from the vertical micro-fluidicchannels around the surface of the stamp. In addition, these channelsserve to allow an exit for the air that must be displaced to push theliquid to the surface of the stamp. An example of a liquid that may beused includes, but is not limited to, water (which will wet the surfaceof the stamp and decrease its adhesivity). In the case of a gas fluid,these surface channels may not be necessary. Examples of gasses that canlower the surface adhesion of PDMS are dimethyldichlorosilane (DDMS),perfluorooctyltrichlorosilane (FOTS),perfluorodecyltris(dimethylamino)silane (PF10TAS), and perfluorodecanoicacid (PFDA), and the like.

In embodiments, the stamp may be operated as shown in FIG. 6. First, itis pressed into contact with a substrate that has the target material ordevices to be picked up. (FIG. 6A). The target material is picked up byVan der Waal's forces between itself and the stamp as is well known(FIG. 6B,C). Target material is placed in contact with the finalsubstrate, and pressed into contact (FIG. 6D). The fluid (for example,water) is pumped to the stamp surface, to reduce adhesion (FIG. 6E). Thestamp may be left in this state (of contact with water) for as long asnecessary for the water to fully wet the stamp surface. Finally, thestamp is removed, leaving the target material behind on the finalsubstrate (FIG. 6F). In FIG. 6A-F, the following labels are made forclarity: fluid inlet 601S; PDMS stamp 602S; fluid distribution reservoir603S; micro-fluidic channels to stamp surface 604S; adhesive stampsurface 605S; devices to be picked up and transfer printed 6; initialsubstrate 607S; final substrate 608S; pump in water 609S so it reachesthe end of the micro-fluidic channels to alter the surface adhesion ofthe transfer stamp and release the devices. Note that any surfacechannels on the stamp surface are not shown in the Figure, and theFigure is not drawn to scale.

Another example of configurations to enable stretchable circuitry are asdescribed in the '125 application in connection with an extendableinterconnect. (See FIG. 3 of the '125 application). The electricalcomponent may be considered as one of a plurality of interconnectednodes, whose interconnections expand/extend as the underlying flexiblesubstrate expands. In embodiments, flexible and stretchable electronicsmay be implemented in a great variety of ways, including configurationsinvolving the substrate, the electrical components, the electricalinterconnects, and the like, and involve electrical, mechanical, andchemical processes in their development and implementation.

As amply discussed herein, CMOS devices offer a variety sophisticatedfunctionality including sensing, imaging, processing, logic, amplifiers,buffers, A/D converters, memory, clock and active matrix switchingtransistors. The electronic devices or the “device islands” of thestretchable/flexible circuitry of the present invention may be devicesand are themselves capable of performing the functionality describedherein, or portions thereof

In embodiments, devices and device islands, devices are to be understoodas “active” as described above.

In embodiments, the electronic devices are optionally laid out in adevice island arrangement, as described herein. The functionalitydescribed herein with respect to circuitry 1000S and thus electronicdevices may thus be present in an electronic device itself, spreadacross arrays of electronic devices and/or device components, orachieved via electronic communication and cooperation with otherelectronic devices and/or device components each electronic device (orelectronic device and device component combination) having separate oradditive, but complementary functions that will become apparent fromthis disclosure. In embodiments, such electronic communication could bewireless. Therefore, said devices may comprise a transducer,transmitter, or receiver capable of such wireless transmission.

Returning to FIG. 1, this figure schematically depicts the functionalityof the circuitry 1000S (and thus the electronic devices, devicecomponents, or combinations thereof). Elements 1100-1700 and their subelements and components including electronic devices, device components,or combinations thereof may be present in the circuitry 1000Sindividually or in any combination as applicable. Certain combinationswill be discussed below; however, the below discussions merely depictexemplary embodiments of the present invention and thus they aretherefore not to be considered limiting of its scope. It will be readilyappreciated that the elements of circuitry 1000S, as generally describedherein, could be arranged and designed in a wide variety of differentconfigurations. Nonetheless, the invention will be described andexplained with additional specificity and detail.

Circuitry 1000S comprises sensors (alternatively termed “sensordevices”) 1100 to detect various parameters of the subject's bodyincluding, thermal parameters such as temperature, and infrared; opticalparameters; electrochemical and biochemical parameters such as, pH,enzymatic activity, blood components including blood gas and bloodglucose, ion concentrations, protein concentrations; electricalparameters such as resistance, conductivity, impedance, EKG, EEG, andEMG; sound, and pressure, tactile, surface characteristics, or othertopographic features of the body. Thus, to achieve the detection of theabove-mentioned parameters, sensors may include thermistors,thermocouples, silicon band gap temperature sensors, thin-filmresistance temperature devices, LED emitters, optical sensors includingphotodetectors, electrodes, piezoelectric sensors, ultrasonic includingultrasound emitters and receivers; ion sensitive field effecttransistors, and microneedles. Exemplary embodiments using one or moreof the above sensors, or detecting and/or measuring one or more of theabove parameters will be discussed below.

The separation distance between sensors (e.g., sensor device islands)can be any that is manufacturable, a useful range may be, but is notlimited to, 10 μm-10000 μm. In embodiments, sensors 1100 can becharacterized as sensor circuits. Individual sensors may be coupled to adifferential amplifier, and/or a buffer and/or an analog to digitalconverter. The resulting sensor circuits may be formed on the same, ordifferent, devices than the sensors themselves. The circuits may be laidout in an active matrix fashion such that the readings from multiplesensors 1100 can be switched into and processed by one or a fewamplifier/logic circuits. Signals from the array of sensors 1100 can beprocessed using multiplexing techniques, including those described inpublished international patent application WO2009/114689 filed Mar. 12,2009 the entirety of which is hereby incorporated herein by reference.Multiplexor component circuitry may be located on or within thecircuitry 10005 on the substrate 200, or at a location that avoidsinterference with the operation of the device such as for example at thebase of a catheter guide wire (which is relevant in embodiments wherethe substrate is a catheter balloon; although other areas that avoidinterference with operation will be apparent.)

Circuitry 1000S comprises processing facility 1200 (alternativelyreferred to herein as “processor”, “processing”, and the terms mentionedimmediately below) which may include a signal processor, digitalprocessor, embedded processor, microcontroller, microprocessor, ASIC, orthe like that may directly or indirectly facilitate execution of programcode or program instructions stored thereon or accessible thereto. Inaddition, the processing facility 1200 may enable execution of multipleprograms, threads, and codes. The threads may be executed simultaneouslyto enhance the performance of the processing facility 1200 and tofacilitate simultaneous operations of the application. By way ofimplementation, methods, program codes, program instructions and thelike described herein may be implemented in one or more thread. Thethread may spawn other threads that may have assigned prioritiesassociated with them; the processing facility 1200 may execute thesethreads based on priority or any other order based on instructionsprovided in the program code. The processing facility 1200 (and/or thecircuitry 1000S in general) may include or be in electroniccommunication memory that stores methods, codes, instructions andprograms as described herein and elsewhere. The processing facility 1200may access a storage medium through an interface that may store methods,codes, and instructions to perform the methods and functionalitydescribed herein and elsewhere. Processing facility 1200 comprised in oris in electronic communication with the other elements of the circuitry1000S including the electronic devices and/or device components.Off-board processing facility 1200A comprises all the functionalitydescribed above; however, is physically separate from circuitry 1000Syet in electronic communication thereto.

Data collection facility 1300 (and off-board data collection facility1300A) are configured to each independently or both collect and storedata generated by the circuitry 1000S and the elements thereof includingimaging facility 1600 (discussed below), and therapeutic facility 1700(discussed below). Data transmission facility 1500 includes a means oftransmitting (RF and/or wired) the sensor information to processingfacility 1200 or off-board processing facility 1200A. Each of theelements 1100-1700 are also configured to be in electronic communicationwith one another and need not necessarily communicate through the datatransmission facility 1500. In embodiments, circuitry 1000S and/or datatransmission facility 1500 is in electronic communication with outputfacility 300 which, in embodiments, can be in electronic communicationwith processing facility 1200A or a separate processing facility. Thevarious outputs described herein, such as visual maps based on sensedparameters, should be understood to emanate from the output facility300.

Circuitry 1000S may be connected or otherwise in electroniccommunication with external/separate devices and systems by physicalconnection, including the methods described above and by providingconductive pads on the circuitry 1000S in an accessible location orlocation that avoids interference with the operation of the device andinterfacing anisotropic conductive film (ACF) connectors to theconductive pads. Also, the circuitry 1000S and/or associated devices10105 may comprise a transducer, transmitter, transceiver, or receivercapable of wireless transmission and thus wireless communication withexternal/separate devices and systems. In addition, circuitry 10005islands may be made to perform optical data communication down awaveguide, such as the one described below.

Power source 400 can supply power to circuitry 1000S in any number ofways, including externally optically, with a waveguide and having PVcells made in a stretchable/flexible format in addition to the rest ofthe circuitry. Alternately, thin film batteries may be used to power thecircuitry 10005, which could enable an apparatus to be left in the bodyand communicate with the operator. Alternately, RF communicationcircuits on the apparatus may not only be used to facilitate wirelesslycommunication between devices within the circuitry and/or toexternal/separate systems, but they may also receive RF power to powerthe circuits. Using such approaches, the need for external electricalinterfaces may be eliminated.

Circuitry 1000S includes therapeutic facility 1700 in embodiments of theinvention, include various elements to effect a desired therapy. Inembodiments, circuitry can comprise heat or light activateddrug-delivery polymers that when activated could release chemicalagents, such as anti-inflammatory drugs, to local sites in the body.Therefore, in embodiments, light emitting electronics (such as LED)could be utilized to activate a drug delivery polymer. Other therapiescan be administered/effected by circuitry 1000S such as circuitryconfigured to deliver ablative therapy to cardiac tissue duringdeployment. Other exemplary embodiments of therapeutic facility 1700will be described herein. Those, exemplary configurations and methodsfor the therapeutic facility are not to be considered limiting of scopeas such should not be considered as uniquely and exclusively applying tothe particular exemplary embodiments being described but rather to allembodiments utilizing a therapeutic facility 1700.

In embodiments of the invention, circuitry 1000S comprises imagingcircuitry 1600. Imaging circuitry 1600 in embodiments comprises a packedarray of active pixel sensors. Each pixel in the array may contain aphotodetector, a pn junction blocking diode, an active amplifier, and ananalog to digital converter, formed in a single piece of singlecrystalline silicon (50×50 μm 2; 1.2 μm thick). In embodiments, Imagingcircuitry 16000 may be encapsulated with a polymer layer such as PDMS toprevent contact stress induced damage. Imaging circuitry 1600 cancomprise an array of photodetectors on the substrate 200 positioned inclose proximity to the site of interest within the subject's body 2000can provide high spatial resolution imaging without the need for alens-based focusing due to the proximity of the photodetectors to thetissue. Imaging circuitry 1600 comprise a light source comprising orconnected to an optical fiber or an LED to provide illumination to thephotodetectors for imaging the tissue of interest.

Thus, the above configuration, designs, and techniques enables thecircuitry to be in direct contact with and in some cases conform to thetissues in the body. Such conformal contact with tissues enhances thecapabilities of the medical devices, methods, and systems disclosedherein.

Exemplary configurations for the circuitry 1000S including sensor 1100,processing 1200 and 1200A, output 300, and therapeutic facility 1700methods, configurations as well as fabrication techniques will bedescribed below and referred to in the following discussion withreference 1000B (and subsequently 1000N, 1000T, and 1000E). However, itshould be understood that any embodiment of circuitry (and therefore itselectronic devices, components, and other functional elements) describedherein in shall apply to any of the exemplary embodiments. The exemplaryconfigurations and techniques are not to be considered limiting ofscope. It will be readily appreciated that the circuitry elements,configurations, and fabrication techniques of the present invention, asgenerally described herein, could be utilized, arranged or otherwiseimplemented in a wide variety of different ways. Also, and by way ofclarification, the circuitry configurations and functional elements aswell as the fabrication techniques described for this (and all exemplaryembodiments) described herein shall be considered to apply to each orany of the embodiments disclosed herein and as such should not beconsidered as uniquely and exclusively applying to the particularexemplary embodiments being described.

FIG. 7 shows an embodiment of the invention wherein circuitry 1000B isstretchable and on an expandable/stretchable substrate 200B which inthis embodiment is an inflatable body. In some embodiments (such as theone shown in FIG. 7) the inflatable body is a balloon on a catheter220B. The skilled artisan will appreciate that the balloon and cathetertogether are referred to as a “balloon catheter” 210B, which is a typeof catheter with an inflatable balloon at its tip and which is usedduring a catheterization procedure for various medical procedures suchas to enlarge a narrow opening or passage within the body. The deflatedballoon catheter 210B is positioned, then inflated to perform thenecessary procedure, and deflated again in order to be removed.

FIG. 7 shows the balloon catheter 210B in a relaxed or deflated state,which is inserted into a lumen 2010B, which in this embodiment is anartery. FIG. 7 also shows arterial plaque 2020B formed on the inner wallof the artery 2010B. The stretchable electronic circuitry 1000B isconfigured in the manner described above with reference to the variousembodiments of stretchable circuitry 1000B and is thus applied to thesurface of the substrate, i.e., inflatable body 200B according to theapplicable techniques described above. In embodiments, the circuitry1000B utilizes complementary metal-oxide semiconductor (CMOS)technology.

FIG. 7A shows a detailed view the circuitry 1000B while the device is ina deflated or unexpanded state. As mentioned above, the circuitry 1000Bof the invention comprises at least one device, which is depicted inFIGS. 7 and 7A as discrete device 1010B. As described above, inembodiments the electronic device is in electronic communication with atleast one other device 1010B. In embodiments, the devices are arrangedin a “device island” arrangement as described herein and are themselvescapable of performing the functionality of the circuitry describedherein including the that which has been described for elements1100-1700 in FIG. 1, the exemplary embodiments below, or portionsthereof. Thus, in embodiments, such functionality of the devices 1010B(or any such electronic device herein) can include integrated circuits,physical sensors (e.g. temperature, pH, light, radiation etc),biological and/or chemical sensors, amplifiers, A/D and D/A converters,optical collectors, electro-mechanical transducers, piezo-electricactuators, light emitting electronics which include LEDs, andcombinations thereof

In embodiments, in order to accommodate the devices 1010B, which may berigid, to the demands of an expandable and stretchable substrate 200Bsuch as a catheter balloon 210B, the devices 1010B are fabricated suchthat they are located in discrete and isolated “device islands” and areelectrically interconnected with stretchable interconnects 1020B, orinterconnects configured to accommodate an expandable or stretchablesurface. As with all elements of the circuitry 1000B, the interconnects1020B can be fabricated according to techniques described herein andthus may be configured differently than what is depicted and describedwith reference to this exemplary embodiment.

In this exemplary embodiment, it can be seen that the interconnects1020B are flexible and thus able to accommodate the stretching caused bythe inflation of the balloon 210B (shown in FIG. 8). Thus, the entiretyof the circuitry 1000B is expandable or stretchable. In the embodimentshown in FIG. 7A, the interconnects 1020B are buckled or non-coplanarwhen the substrate 200B is in a deflated state. When inflated (as shownin FIG. 8), the interconnects 1020B become either coplanar ornon-buckled so as to accommodate the increased distance between thedevices 1010B upon inflation. Such buckling, non-coplanar interconnects,as well as circuitry having similar properties, are described elsewhereherein and apply.

As mentioned above, in embodiments, the electronic communication betweenthe devices and/or between said devices and separate (external, forexample) devices could be wireless. Therefore, said circuitry 1000Band/or associated devices 1010B may comprise a transducer, transmitter,or receiver capable of such wireless transmission.

The specific fabrication method for such circuitry may depend on thespecific circuit classes desired to incorporate into the device, and thespecific characteristics of the circuitry, including those of thedevices, the interconnects, etc., and include, but is not limited to,those disclosed with respect to this exemplary embodiment. Anon-limiting example of the complete fabrication steps of an exemplaryembodiment of the invention, i.e., a catheter balloon instrumented withtemperature sensors, is described in the following paragraphs. It shouldbe noted that while the embodiment described below refers to aninflatable system (specifically a catheter balloon), the skilled artisanwill appreciate that such principals of operation will apply tosituations where the substrate on which the circuitry is applied isotherwise stretchable or expandable but not inflatable, or where thesubstrate is inflatable but not necessary stretchable as described abovewith reference the FIG. 1 and the discussion of substrates.

In embodiments herein including but not limited to those describedherein for balloon catheters, a neural bundle prosthesis, endoscopy, andtissue screening, the arrays of devices, which may include temperaturesensors and associated differential amplifiers, buffers, A/D converters,logic, memory, clock and active matrix switching transistors are laidout in a “device island” arrangement. The device islands can be 50 μm×50μm squares, most of which accommodate a single conventional sensorcircuit, e.g., one a temperature sensor, connected to a buffer, thatitself connected to an amplifier. The temperature sensor, which may beresistive, diode-based, etc., as described in greater detail below,supplies a signal that reflects temperature (or a temperature change),and the remaining sensor circuitry conditions the signal for subsequentprocessing.

In embodiments herein including but not limited to those describedherein for balloon catheters, a neural bundle prosthesis, endoscopy, andtissue screening, devices accommodate active matrix switches and A/Dconverters for transforming an analog temperature signal into digitalform, and some devices accommodate logic circuitry capable of reading indigital signals and processing them (e.g., to assign a value to thesensed temperature or temperature change). These circuits may output thetemperature reading to another module or, and are capable of outputtingdata or storing it in on-board memory cells.

In embodiments herein including but not limited to those describedherein for a balloon catheter, a neural bundle prosthesis, endoscopy,and tissue screening, the circuitry is arranged and designed such thatpreferably only about one, but not more than about 100 electricalinterconnections are required between any two device islands. Inembodiments, the circuitry is then fabricated on an SOI wafer (althoughit should be understood that standard wafers could be used)(1.2 μm thicktop Si, 1 μm thick buried oxide) using standard CMOS fabricationtechnology, and the silicon space in between each island is etched awayto isolate each island. The circuits are protected by a polyimidepassivation layer, then a short HF etch step is applied to partiallyundercut the islands. The passivation layer is removed, and then a thinfilm of SiO2 is deposited and patterned (100 nm thick) by PECVD or otherdeposition technique combined with a liftoff procedure, such that theoxide layer covers most of the space between devices (a/k/a deviceislands) except for a region around each device island that is about 5μm wide. Another polyimide layer is spun on and patterned into the shapeof the interconnects. Typically one interconnect may extend from thecenter of one device to the center of another device. Alternately, twointerconnects may extend from each corner of the device to two differentdevice corners. Alternatively, one interconnect may extend from thecenter of one island edge to the center of another island edge. Theinterconnect bridges may be about 25 μm wide and may accommodatemultiple electrical lines. The polyimide partially fills where thedevice island is undercut; this serves to stabilize the island later inthe release process and to prevent its migration. VIAs are etched intothe PI layer to allow metal wires, patterned in the next step, tocontact the circuits and connect one island to another. (This step canbe repeated to form additional sets of wires located above the firstset). Another PI layer is spun on (covering the wires and everythingelse). The PI (both layers) is then isolated by etching with a depositedSiO2 hard mask, in O2 RIE. PI located outside the devices and bridges isetched, as well as PI covering areas that are meant to be externallyelectrically interfaced, and small areas leading to the underlyingoxide. Etch holes may be formed if necessary and then transferredthrough the silicon or metal layers by wet and/or dry etching. Theunderlying buried oxide is etched away using HF etchant to free thedevices, which remains attached to the handle substrate due to the firstpolyimide passivation layer which contacts the handle wafer near theborder around the devices.

If the HF etch is not controllable enough and seeps under the PIisolation layer and thereby attack the CMOS devices, then prior to thefirst PI passivation of brief Argon sputtering can be done to remove anynative oxide followed by amorphous silicon sputtering followed by the PIpassivation and the rest of the processing. After rinsing, the devicesare left to air dry.

In connection with some embodiments, after drying, they are picked upwith a PDMS stamp, and transfer printed onto either the surface of thesubstrate, which in this particular exemplary embodiment is aninflatable body such as a catheter balloon 210B, or a surface of theinflatable body coated with a thin PDMS layer, or a separate thin PDMSlayer (that may later be wrapped around the inflatable body). FIG. 9Ashows a side view of a balloon with the PDMS layer 230B wrapped aroundthe surface of the balloon. FIG. 9B is a cross-sectional view whichshows the catheter 220B, the surface of the balloon 210B, and the thinPDMS layer 230B applied to the balloon.

It is also possible for a thin PDMS mold to be made of half the(inflated) balloon shape (in embodiments involving an inflatable body),such that it can be stretched flat, and have circuits transferred ontoit in the flat state, and then released to pop back into thehalf-balloon shape; this half-balloon can then be easily attached to thereal balloon, and may even be glued. It is noted that in some caseswhere the circuits are on the outside of the balloon, the bridges (alsoreferred to as interconnects and physical electrical connections herein)pop or buckle outward when the devices are compressed or theexpendable/inflatable body is otherwise in a relaxed or deflated state.In the inflated state, the bridges 1020B should be fairly non-buckledand/or coplanar with the surface of the substrate 200B so that in thedeflated state they can buckle to accommodate the significantcompressive stress.

Alternately, this process can be repeated with a mold made in thedeflated state of the balloon, and stretched beyond flat so that it issignificantly expanded, such that after the circuits are transferred andthe mold is released, they compress significantly. In this case, theyshould be compressed enough so that after transfer to the actualballoon, when it is fully expanded, the bridges are nearly flat or fullyextended and almost non-buckled.

In embodiments where the circuitry 1000B is directly transferred to theballoon, the PDMS stamp should be made thin (−100-500 μm in thickness)and thereby compliant enough to conform to the shape of the balloon.

In embodiments where the circuitry 1000B is first transferred to aseparate thin PDMS layer, the PDMS layer may be on a rigid substrate sothat the transferring can be done easily. Then the PDMS layer can bepeeled off the substrate and wrapped around the balloon 210B either inthe inflated or deflated state, depending on whether the circuitry 1000Bwas transferred with any prestrain or not. It may be desirable to makethe circuitry in a 1D array rather than a 2D array. In this way, thethin PDMS layer is a long, narrow ribbon that can be easily wrappedaround the balloon 210B so as to cover the entire balloon 210B surface.

In embodiments, to apply the circuitry, the balloon 210B can be directlyrolled along a planar array of circuitry 1000B on PDMS carrier substrate204B as shown in FIG. 10A. The balloon can be subsequently deflatedand/or re-inflated. Deflation can cause the interconnects in thecircuitry to buckle and take on compression forces imposed by deflationas shown in FIG. 10C, while inflation causes the interconnects to besubstantially coplanar with the substrate (as shown in FIG. 10B). Thisprinciple applied to inflatable, stretchable, and flexible embodimentsherein. Further, it should be understood that the described stampingmethodologies applied to the balloon catheter can be applied to stampthe electronic circuitry in all of the embodiments described herein.

In embodiments circuitry may be encapsulated (in embodiments, while inits compressed state) with another layer of PDMS, or a liquid layer ofPDMS followed by an upper layer of solid PDMS to make a fluidencapsulation.

In embodiments where the circuitry is facing outwards on the balloon, itmay be electrically externally interfaced at conductive pads that shouldbe designed to be located at the base of the balloon. Anisotropicconductive film (ACF) connectors can be used to interface to theseconductive pads, by pressing and heating the film onto the pads. Thefilm can then run down the length of the catheter since it is so thinand flexible.

In embodiments where the circuitry is encapsulated or facing inwards,they may be electrically externally interfaced by first removing part ofthe encapsulating polymer over the conductive pads through wet or drychemical etching, or physical mechanical removal of material, includingbut not limited to drilling. At this point, the ACF may be incorporated.Alternatively, the stretchable circuitry may be electrically interfacedto an ACF prior to the transfer or encapsulation process.

As described above, in embodiments the circuitry is powered externallyoptically, using the catheter tube as a waveguide and having PV cellsmade in a stretchable format in addition to the rest of the circuitry.In addition, LED islands may be made to perform optical datacommunication down the catheter waveguide. Alternately, thin filmbatteries may be used to power the circuitry. Alternately, RFcommunication circuits on the device may be used to wirelesslycommunicate outside of the body, and may also receive RF power to powerthe circuits.

In embodiments, the substrate is polymeric, e.g., polyimide orpolydimethylsiloxane (PDMS). The single-crystal semiconductor devicesthemselves may be created on a silicon-on-insulator (SOI) carrier waferin accordance with a circuit design implementing the desiredfunctionality. Interconnect systems (as described herein) may also becreated during this step to join smaller device islands. The processedsingle-crystal devices are removed from the SOI wafer (e.g., by etching)and are then placed in contact with an elastomeric stamp for transferprinting (via methods described herein) onto the desired flexiblepolymer substrate. In embodiments, the circuitry 1000B is transferredonto the stretchable substrate, which may be pre-stretched prior totransfer. In embodiments, the stretchable substrate serves as thecatheter balloon 210B, and can be conformed to the shape of an inflatedballoon by a mold. The balloon polymer can be stretched over largestrains (greater than 300%) of its relaxed or native state withoutcausing damage to the circuitry 1000B. As described herein, thecircuitry can be encapsulated including with additional thin polymerlayers to provide further protection from cracks or local contactstresses.

In an apparatus of the present invention involving but not limited tothe exemplary embodiment of the balloon catheter presently beingdescribed, the substrate (in this embodiment, a catheter balloon 210B)is covered with stretchable circuitry 1000B having an array of devices210B and may be inserted in a lumen 2010B of the subject's body. Thedevices may include temperature sensors. The temperature sensors may be,for example, silicon band gap temperature sensor, consisting of silicondiodes. The forward voltage of these silicon diodes are sensitive tochanges in temperature. Alternatively, platinum thin-film resistancetemperature devices (RTD), which measure temperature based ontemperature-induced changes in electrical resistance or thermocouplecircuits that sense temperature changes between different thermoelectricmaterials can be utilized. For thermal resistors, the normalized changesin resistance (R), temperature coefficients of resistors (a), arerelated to the change in temperature (T) by

ΔR/R=αT.

Platinum (500 Å) and an adhesion layer of chromium (150 Å) can bepatterned and deposited on SOI wafers using thermal evaporation viae-beam to define individual RTD sensors. The RTD sensors can beintegrated with CMOS based amplifiers, transducers, computation logicelements, and A/D circuitry on the same device islands as previouslydescribed.

Once the circuitry 1000B is transferred onto the inflatable body in thisembodiment, a balloon catheter 210B, stretching and fatigue tests can beperformed with a mechanical bending stage, capable of applying uneasilytensile or compressive strains in multiple directions or by repetitiveinflation and deflation loading cycles. The mechanical bending stagescan work in parallel with electrical probing stations (Agilent, 5155C)that are coupled to the circuit semi-conductors. In embodiments, toevaluate the performance of the circuitry, multiple cycling of heatingand cooling tests can be performed. The circuits can be heated to 160°C. for 5 min. and subsequently cooled down before and after eachelectrical measurement.

In this exemplary embodiment and in others where it is desirable toprotect the circuitry from external damage, an encapsulating thin layerof polymer can be applied to the circuitry, including on the surface ofthe inflatable body after the circuitry is applied thereto according tothe description below and other applicable encapsulation methodsdescribed herein. This encapsulating polymer layer may be extremely thin(<100 um) and photocurable in order to allow selective curing in regionswhere direct contact with sensors is not required. Thus, areas of thedevice that do require direct or conformal contact with the tissue ofinterest may be exposed. Such selective encapsulation is describedbelow, but any technique for selective encapsulation described hereinmay apply. It should be noted all methods of selective encapsulationapply to any embodiment disclosed herein.

In embodiments, the RTD temperature sensors may be preferentiallyexposed for direct contact during photocuring. There are severalpolymers that may be used for preferential photocuring of theencapsulating layer, including but not limited to polyethylene glycol(PEG) with 2-hydroxy-2-methylpropiophenone photoinitiator. Thephotocurable PEG encapsulation cures once it is exposed to ultravioletlight. Photomasks designed using AUTOCAD can be printed to allowpreferential curing of the surface of the inflatable body. These maskscan be inserted as a filter into a UV light source stage coupled with awide excitation UV filter. Exposure with an aligned mask enablespolymerization in strategic regions of the inflatable body. Visualalignment during polymerization can be achieved with a CCD camera.

In embodiments, the substrate (in embodiments an inflatable body such asa catheter balloon 210B) is instrumented with an array of devices 1010Bcomprising sensors such as temperature sensors can be deployed such thatthe temperature sensors are positioned in direct contact and orconformal with the surface of plaque in the lumen upon inflation of theinflatable body.

An important advantage realized in this embodiment, and in otherembodiments having the flexible and/or stretchable circuitry describedherein is that the circuitry (and thus its devices such as sensors) cannot only come into direct contact with the surface or tissue of interest(in this case, the plaque and inner surface of the lumen), but alsoachieve conformal contact with the contours and/or surface features ofthe surface or tissue so as to achieve greatly improved performance.

In embodiments, the separation distance between sensors can be any thatis manufacturable, a useful range may be, but is not limited to, 10μm-10000 μm. Individual sensors may be coupled to a differentialamplifier, and/or a buffer and/or an analog to digital converter. Thesecircuits may be formed on the same, or different, devices than thetemperature sensors. The circuits may be laid out in an active matrixfashion such that the readings from multiple temperature sensors can beswitched into and processed by one or a few amplifier/logic circuits.These sensor arrays record input signals that can then be channeled fromthe surface of the balloon to guide wires and a processor using metalelectrodes deposited near the junction between the balloon surface andthe catheter tubing. Alternatively, gold metal wires may be used toattach the balloon circuitry to the surface of the catheter guide wireusing a wire bonder. Signals from the array of sensors can be processedusing multiplexing techniques, including those described in publishedinternational patent application WO2009/114689 filed Mar. 12, 2009 theentirety of which is hereby incorporated herein by reference.Multiplexor component circuitry located in the base of the catheterguide wire can facilitate this type of data analysis/processing.

Such multiplexing techniques disclosed herein allow for the circuitry(or an operator) to select which active devices should be utilized, orwhat pattern of active devices should be functioning. Processingfacility is configured to generate a user interface on output facilitysuch that the operator may make said selections or adjustments. In somecases the identity or pattern of active devices being utilized is basedupon whether (or the degree to which) the devices are in electrical orconformal contact with the tissue of interest. Thus, all embodimentsherein are able to generate useful amounts of data even when allelectronic devices are not in complete contact with the area of intereston the tissue, but may only be in partial contact.

The device operator may use optical guidance during an x-ray angiographyto deploy the balloon catheter once the guide wire reaches the region ofthe plaque location. The deformable and stretchable nature of thecatheter balloon allows temperature measurements at multiple contactpoints on non-uniform surface contours such as that of arterial lumenand deposited plaque (shown as 2020B in FIGS. 7 and 7A). (The conformalcapabilities of the circuitry enable such abilities). Once deployed, theprocessing facilities described herein process the transmitted signalsand produce a spatial temperature map of the plaque in the lumen. Thisdata can be used by the device operator to detect temperatureheterogeneity presence along the plaque and determine plaque type. Onceplaque type is determined and surface contours are characterized, theballoon catheter can be deflated and removed.

In another embodiment of the invention, the stretchable circuitry 1000Bcomprises pressure sensor arrays. Such sensor arrays may besilicon-based and utilize piezo-resistive or capacitive sensing, or maybe polymer based or optically based. In embodiments, a pressure sensorhas a working range and size suitable to the application, and should beamenable to application as described herein and tolerant to thestretching forces it will experience.

FIG. 10D shows one exemplary pressure/contact sensor which may beutilized with any embodiment described herein requiring a pressuresensor or contact sensor. The pressure sensor comprises a flexible andsuspended diaphragm 600 of a flexible material such as thinsingle-crystal silicon, polysilicon, and/or silicon nitride thin film.The diaphragm 600 can be suspended directly above a base layer of dopedsilicon consisting of a metal electrode layer extracted from an SOIwafer. The polysilicon diaphragm layer may be formed as a suspendedlayer by first depositing an SiO2 layer on the silicon electrode 610.The polysilicon may then be deposited on the SiO2 layer, which in turncan be selectively etched. This etching step allows for the formation ofa suspended and flexible polysilicon structure. In order to producediaphragms with a controlled thickness, precise etch rates using HF mustbe used. This diaphragm with known thickness (2-10 μm thick), materialmodulus, and surface area and the underlying silicon electrodecollectively form a parallel-plate capacitor. The sensor capacitance isa function of distance between the top polysilicon layer and theunderlying silicon electrode. The capacitance recordings relatediaphragm deflection (caused by force P) to changes in capacitance.

In embodiments of the invention, the stretchable circuitry comprises anarray of contact sensors. The contact sensors are designed to provide anon/off electrical resistance change in response to a pressure, such thatwhen the applied pressure exceeds a predetermined threshold, the sensorprovides an electrical signal indicating that it is in contact with,e.g., the arterial wall. One example of how to form a contact sensor isto make a simple mechanical-electrical switch, in which one conductor ismechanically pressed onto another conductor. The lower conductor,located on the surface balloon, consists of a metal wire that isnon-continuous in one or more places to form an open circuit.Encapsulated around this open circuit is a diaphragm formed out of PDMS.The PDMS may be molded or etched into a diaphragm shape. The upper wallof the diaphragm is coated with a metal conductor, by standard means ofphotolithography patterning, electrochemical etching, etching, shadowevaporation, etc. The diaphragm is aligned and bonded to the surface ofthe balloon. The diaphragm is designed so that when a certain pressureis applied, it bends down to allow the upper conductor to contact andshort-circuit the lower non-continuous conductor. This is done bycontrol of the geometry (height and width) and materials of thediaphragm. In yet another non-limiting example, the diaphragm may bemade with MEMS techniques, such as sacrificial silicon dioxide layerswith a polysilicon bridge on top.

In embodiments of the invention, to measure relative pressure, eachpressure sensor can be coupled with reference sensor unit, which hasidentical electrical characteristics except for a significantly lowerpressure sensitivity. Difference in pressure measurements between thesensor and the reference unit enable compensation for many parasiticeffects. The reference units may be created by leaving a passivationlayer on the top surface of the polysilicon electrode. Having areference unit along with a pressure sensor unit allows for differentialpressure recordings. Once deployed, such sensor arrays can generate datathat can be used by circuitry to determine, among other things, thepresence and mechanical properties of the tissue such as the presenceand properties of an arterial lumen and plaque therein. In embodimentswhere the substrate is a balloon, such data may also be used to estimatethe diameter of the balloon and the lumen and provide feedback to thedevice operator to end balloon inflation at this point. This type ofsensing can be combined with temperature sensor arrays to provide athorough assessment of tissue mechanical and thermal properties during asingle deployment attempt.

In embodiments, data generated by such pressure sensing also allows forcreation of a tactile image map of the surface contours of materialssuch as arterial plaque. Further, this type of mechanical imaging inballoon catheter embodiments can indicate whether a stent has beensuccessfully deployed when the balloon is inflated.

In embodiments of the invention including a therapeutic facility 1700,plaque type is initially determined with data generated by temperaturesensors and immediately afterwards, drug-delivery polymers and circuitryembedded in the balloon polymer are activated to cause local coolingand/or release of chemical agents, such as anti-inflammatory drugs, tolocal sites on the plaque where inflammation is present. In embodiments,therapeutic facility 1700 comprises light emitting electronics (such asLED) could be utilized to activate a drug delivery polymer.

In embodiments of the invention, circuitry comprises imaging circuitry(referred to in connection with FIG. 1 as 1600). Imaging circuitrycomprises packed array of active pixel sensors. Each pixel in the arraymay contain a photodetector, a pn junction blocking diode, an activeamplifier, and an analog to digital converter, formed in a single pieceof single crystalline silicon (50×50 μm 2; 1.2 μm thick). In embodimentson an inflatable body such as a catheter balloon, all of the circuitrymay be encapsulated with a polymer layer such as PDMS to prevent contactstress induced damage of circuitry on the inflatable body, since thereis no requirement for direct contact of the lumen with photosensorarrays. An array of photodetectors on the inflatable body positioned inclose proximity to the plaque site within a the arterial lumen canprovide data used by processing facilities to create high spatialresolution images without the need for a lens-based focusing due to theproximity of the photodetectors to the lumen. The catheter guide wiremay comprise a light source, such as an optical fiber or an LED toprovide illumination to the photodetectors for imaging the plaque andlumen surface.

In embodiments of the invention, the substrate is covered withultrasound emitters and receivers to generate data used to produce alateral deep-tissue image of the plaque and arterial lumen.

In embodiments of the invention, substrate is covered with stimulatingand recording electrodes used for measuring plaque conductivity. Sincevulnerable plaque is significantly less conductive than stable plaqueand arterial tissue, this form of sensor array can help determine theplaque type based on measured conductivity of the plaque. Once theinflatable body is deployed, the electrodes are positioned in directcontact and/or conformal with the plaque deposits and electricalconductivity is measured. Again, this device can be combined with othersensor array types embedded in the stretchable inflatable body toprovide multiple sensing and therapeutic functionalities in parallel.

Data collected by sensors at the site of the plaque can be interpretedagainst a baseline established by deploying the same inflatable body (ora second inflatable body on the same catheter) at a different location,which is free of plaque, in the lumen.

In embodiments of the invention, the array of devices includestemperature detectors, pressure sensors, and photodetectors collectivelyfabricated in a flexible and stretchable polymer-based balloon cathetersubstrate. These active device components can be designed using 0.6 μmdesign feature resolution or smaller. They may be integrated on thedevices that are pieces of single crystalline silicon (50×50 μm 2; 1.2μm thick). Once the balloon is inserted in the arterial lumen, thedevice operator navigates the guide wire leading the balloon to theplaque location. The deployment of the balloon can stop blood flowintermittently. The guide wire is preferably fitted with an opticalfiber or LED; the close contact of the imaging arrays to the lumenavoids the need for optical lens arrays, since light from the opticalsource may pass through the interconnect gap regions between the arrays,scatter through the lumen/plaque, and reach the photodetectors directly.

In this embodiment, the pressure sensor array detects when theinflatable body initially contacts the plaque and generates data used tospatially map the entire region of contact to ensure successfuldeployment. Circuitry continuously record data generated by the sensorsand spatially maps temperature as a way to detect where in the arterialplaque there may be inflammation and macrophage deposits. The deviceoperator may examine the data and decide whether to take immediateaction through drug-delivery measures, stent deployment, or furthertests on the plaque. The device operator may also utilize light imagingto visualize the plaque. Having integrated pressure sensors and imagingsensor arrays on the balloon, in addition to temperature sensors, allowsfor creation of a detailed tactile, thermal and visual map of theregions where the balloon contacts the plaque. This type of distributedmechanical sensing and imaging with an array of pressure sensors andphotodetectors ensures that the stent and/or balloon contact the entiresurface of the plaque.

In embodiments, the lumen may be a pulmonary vein. In such embodiments,the circuitry 1000B comprises devices having sensors that generate datarelated to the electrical activity of the pulmonary vein which in turncan be used processing facility to generate maps of the circumferentialelectrical activity of the pulmonary veins. In other embodiments, thesensor may include active electrodes. Such embodiments may generate datafor mapping electrical activity of the pulmonary vein. Further,embodiments may also include a pressure sensor and temperature sensorfor heterogeneous sensing on a balloon to be deployed in the pulmonaryvein for mapping electrical activity. Such embodiments described for thepulmonary vein may apply to any lumen. While in other embodiments, thesensor may include active electrodes for generating data used formapping electrical activity of the septal wall, atrial wall or surfaces,and/or ventricular surfaces.

Other embodiments may include active electrodes configured to generatedata to map electrical activity while the inflatable body is inflatedallowing concurrent mapping and ablation. In embodiments, ablation maybe effected cryogenically, via laser or via RF energy.

In other embodiments, a contact pressure sensor device generates dataused by processing device maps force per unit area applied to the ostiumof the pulmonary vein which can be used for occlusion of the inflatablebody, i.e., balloon, during mapping and ablation.

The inflatable body herein may be inflated with fluid of specifiedtemperature. Data related to the temperature of the fluid may begenerated by circuitry and thus used to tune the heat output of theelectronics, or to calibrate the sensors.

Embodiments, of the balloon catheter can be deployed with a stent thatmay be fitted around the active sensing and imaging regions of theballoon.

Embodiments utilizing a catheter may utilize the inventive catheterdescribed herein. FIG. 10E shows a catheter 7000 comprising threelumens: guide wire lumen 7002 (houses the guide wire); fluid injectionlumen 7006 (channel for fluid which will be used to inflate balloon andor control temperature of the electrodes or active devices on theballoon surface); and the circuitry lumen 7004 (houses the flexible PCBand wiring which will be connected to the DAQ). In the assembly of thecatheter system, the flexible PCB is wired for connection to the DAQ andalso electrically connected to the stretchable electrode array. Thisunit is then threaded into the circuitry lumen, of the tri-lumenextrusion as illustrated in with the DAQ-bound wires entering first andexiting through the proximal end of the catheter for connection to theDAQ.

An embodiment of the multiplexer is described in connection with theballoon catheter exemplary embodiment; although it should be understoodto apply to other embodiments. FIG. 1OF shows a Wireless catheterstatistical multiplexer that concentrates 16 (but could be othernumbers) asynchronous channels over a single radio link. In FIG. 10E,10-115 are the balloon catheter electrodes. 3 cross point switches areused for multiplexing. After the mux, an X time's amp is employed. Thisis feed into the A/D of the CPU and then transmitted wirelessly. Twowires are needed for power and ground (3-5V @ 5-7.5 mA).

The asynchronous ports can be individually set for speeds to 57.6 Kbps.Hardware (CTS/Busy high or low) or software (Xon/Xoff even, odd, mark,space or transparent) flow control is also set on a port by port basis.

The Wireless catheter statistical multiplexer composite is a wirelesslink that runs at 57.6 Kbps. It transmits on the license-free ISM orMedRadio band. The link radio modules are easily configured using aterminal or PC connected to the network management port or port one. Therange is 4-6 feet or up to 1000 feet with optional external repeater,not shown.

The network management port includes local and remote configurationcommands. The Show Configuration Commands allow the system manager toview the configuration settings of both the local and remotemultiplexers. Network management features include port and compositeloopbacks, capture of a remote or local port, send a test message to anindividual local or remote port, set multiplexer ID for nodeidentification and a built-in “data line monitor” which allows themonitoring of the transmit or receive lines at the local multiplexer. Aunique feature of the multiplexer is the Copy Command. This commandallows a trainer at the host site to “copy” any local or remote port toview exactly what the user is entering.

Such multiplexing techniques allow for the circuitry (or an operator) toselect which active devices should be utilized, or what pattern ofactive devices should be functioning. In some cases the identity orpattern of active devices being utilized is based upon whether (or thedegree to which) the devices are in electrical or conformal contact withthe tissue of interest. Thus, all embodiments herein are able togenerate useful amounts of data even when all electronic devices are notin complete contact with the area of interest on the tissue, but mayonly be in partial contact.

Referring back to FIG. 1, another embodiment of the present inventioninvolves a substrate 200 (denoted as 200N with reference to certainembodiments below) which is, or which comprises, a prosthetic devicewhich can be inserted by means of a small opening, between severed endsof a nerve bundle. The external surface of the prosthetic device isprovided with circuitry according to the disclosure herein wherein thecircuitry comprises microelectrodes coupled with amplification andstimulating circuitry.

The prosthetic device can be stretched, inflated or otherwise expandedto conform to the shape of the nerve bundles. This expansion mayfacilitate the orientation of microelectrodes, strategically positionedon the device, in such a manner as to bridge gaps in nerve bundles.Moreover, circuitry (and in embodiments therapeutic facility 1700) mayselectively create connections between a plurality of nerves with thehelp of onboard logic components or by manual input from an operatorutilizing an external device interfaced to the circuitry in the mannersherein described. The execution of these actions may occur withoutmovement of electrodes or further physical intervention.

The benefits of this particular embodiment include the ability toelectrically reconnect many individual nerves without the need tomanipulate them directly, reduce risk of aggravation to nerve damage byusing a minimally invasive procedure and its ability subsequently“rewire” the connections one or more times without further surgicalprocedure. Additionally, this embodiment has the advantage of employingsignal amplification and conditioning to adapt the input and output ofeach “reconnection” to the characteristics and function of a specificnerve fiber.

In this embodiment, circuitry is fabricated according to the methodsdescribed above. It should be noted that like other embodimentsdescribed herein, devices can be laid out in a device “island”arrangement. The devices are ˜50 μm×50 μm 2 squares, most of whichaccommodate one or more components connected to a buffer and also to anamplifier. Some devices accommodate active matrix switches and A/Dconverters, and some islands accommodate logic circuitry capable ofreading in digital signals and processing them, and are capable ofoutputting data or storing data in memory cells. Circuitry may alsocontain device components which comprise metal contact pads. Thecircuits on devices are configured and designed such that preferablyonly about one, but not more than about 100 electrical interconnectionsare required between any two device islands or devices.

In embodiments, substrate comprises an elastomeric vessel (which is alsoreferred to herein as an “inflatable body”). In certain embodiments suchsubstrate is in the shape of a disk, said vessel covered with flexibleand/or stretchable circuits described herein and having a multitude ofelectrodes. The disk can be deformed to enable its passage through asmall opening in a “deflated” configuration and subsequent deployment inthe gap between severed or damaged nerve bundles. Inflation with aviscous fluid is preferable, but it should be clear that a variety ofgases, fluids or gels may be employed. According to the methodsdescribed herein, the flexible and/or stretchable circuitry is sealedwith the miniature electrodes exposed so as to enable them to interactwith the surrounding tissue. Each electrode can serve as either asensing electrode or a stimulating electrode, and is connected to eithera sensing or stimulation amplifier depending on device configuration.Signals are routed from sensing electrodes through signal processingcircuitry to stimulation electrodes. In this embodiment, any electrodecan act as a stimulating or a sensing electrode, depending on thedynamic configuration in effect at the time. Such electrodes maygenerate data while in electrical contact and/or direct physicalcontact. “Electrical contact” in meant to encompass situations where theelectrodes are generating data regarding a tissue of interest while notnecessarily being in direct physical contact. It should be noted that,“functional contact” or “sensing contact” is similarly meant toencompass situations where the sensing devices are generating dataregarding a tissue of interest while not necessarily being in directphysical contact.

FIG. 11 shows the path of a single nerve pulse in an exemplaryembodiment of the invention. Electrode 1022N is in contact with nerveending 2030N at a given location on the surface of the device.Electrical activity affects the current or potential at the electrodeand is amplified by the sensing amplifier 1012N and then optionallyundergoes further signal conditioning by block 1014N. From there, theelectrical signal flows to the multiplexer 1016N which is configured tomatch nerve-signal sources and destinations in a way most beneficial toclinically desirable outcomes. The multiplexer 1016N dispatches thesignal to the appropriate location on the other side of the device,where it is again amplified by the stimulation amplifier 1013N andfinally effects nerve activity of nerve ending 2032 through electrode1024N. FIG. 12 shows a circuit diagram showing multiple channels for theembodiment just described,

Preferred embodiments contain thousands of such paths, enabling theinterconnection of many nerves across a nerve gap in aflexible/configurable manner. Notably, the connection between two endsis not determined by the position of the device or at the time ofimplantation, it can be altered during the procedure or at any timethereafter by altering the dimensions of the invention. Among thereasons for altering the routing of the nerve signals would beobservations about mappings of the various nerves, progress of thepatient's recovery or effects of neuro-plasticity, or shifts in therelative positions of electrode and tissue in the course of motion orphysiological processes. One automated means of configuring theapparatus is as follows.

As shown in FIG. 13, on initial deployment, all electrodes andassociated amplifiers are set to be in sensing mode 3010. Electrodesthen detect data of the potentials 3020. Electrodes are individually andcollectivity affected by the activity of the nerves next to them. Theseare then amplified and processed (by any applicable processing facilitydescribed herein) to determine the presence or degree of electricalactivity 3030, which is then used to configure the channels in thefollowing manner: as shown in step, 3040 electrodes those regions withhigh electrical activity are left in sensing mode. Step 3050 shows thatelectrodes in regions with less, but non-zero, activity are switched tostimulation mode. In step 3060, electrodes in regions with no activityare turned off to conserve power and avoid interference. The full natureof the electrical signals, including their amplitude and frequency, areoptionally utilized by this embodiment to deduce the original anatomicalfunction of the nerve tissue it is contacting.

In embodiments, circuitry makes measurements of conductivity betweenelectrodes. These measurements correlate with the electrical activity ofphysiological structures and hence can be used by circuitry or externalprocessing facility 1200A to create a contour map of conductivity. Inembodiments, such map can be used to enhance the configurations of theelectrodes and multiplexing strategy.

As mentioned elsewhere herein, sensors can also include temperature orpH sensors or orientation sensors, and the measurements obtained fromthem used to improve the connections.

In other embodiments, the device does not simply provide one-to-onecorrespondence of electrodes. Stimulation of a given output electrodecan be based on signals from more than one sensor and/or more than oneinput (sensing) electrode, or the stimulation of many electrodes basedin signal from just one input electrode.

After initial configuration, the disclosed invention can be reconfiguredone or more times thereafter, by establishing a wireless control link tothe device from outside of the body (in the manners described herein)and using additional information to make decisions about the bestconfiguration. For example, the clinician can communicate with thepatient, asking him or her to attempt to move certain muscles, or toreport absence or presence of certain sensations. Since as mentionedabove, the substrate is biocompatible, the reconfigurations can be doneafter a surgical incision has successfully healed and without anesthesiaor further trauma to the patient, enabling the connections betweennerves to be slowly optimized for maximum benefit over a period of time.The benefit of the present invention is that these adjustments do notrequire any physical or surgical manipulation, thus avoiding furtherrisks and suffering to the patient. Furthermore, subsequentconfigurations can be integrated into a comprehensive rehabilitationprogram.

The circuitry is distributed throughout substrate, which provides a highdensity of electrodes while allowing the invention to be realized in avariety of sizes and shapes most advantageous to a specific anatomicallocation. The flexible/stretchable nature of the circuitry enables it toachieve—and maintain—close contact with irregular surfaces of transectednerve fibers, providing a significant advantage over electrode systemsthat have to be individually positioned or require nerves to be flatplanar surfaces that are not usually found in nature. In addition tomaking initial contact possible without either explicit surgicalplacement (which would be impractical for thousands of individualnerves) or perfectly flat surfaces, the present invention has thebenefit of maintaining contact (electrical or physical) with a largenumber of nerves despite physical movement, physiological processes(such as inflammation or scarring), or the passage of time, since anear-uniform pressure is applied to all of the electrodes by the fluidfilling the apparatus.

FIG. 14 shows the device implanted in the spine of a subject havingneural damage. 2036N and 2037N are vertebrate of a spine. Cartilaginousdisc 2038N disc is also shown. Inflatable disk 212N having circuitry1000N is shown being inserted into the area of damage. Once in place,disk 212N is inflated thus contacting the nerves as described above.

Other embodiments could include a therapeutic facility (such as 1700described in FIG. 1) invention would also incorporate drug deliverycapabilities alongside electrode arrays. FIG. 15 shows such anembodiment. Circuitry 1000N comprising electrodes 1022N, for example, isprovided on the outside surface of disk 200N, which may or may not beinflatable. A drug reservoir 214N is provided ,which communicates withthe surface of the disc 200N by way of channels 216N. At the end of thechannels 216N are valves 218N which in embodiments are MEMS valves,which are connected to and controlled by circuitry 1000N which comprisesthe therapeutic facility 1700. Refill line 219N is connected to thereservoir which allows for the reservoir 214N to be refilled inembodiments. One benefit of such a capability is to deliver drugs toreduce rejection or scar formation at the interface between the tissueand the apparatus. The release of a drug can be controlled by means ofthe MEMS valve 218N and delivered only in areas where processingfacility 1300 has determined, by being so configured, that previousmeasurements (such as temperature or conductivity) have indicated thatit may be of greatest benefit. Other embodiments include individualcavities containing the drug, which when consumed necessitate thereplacement of the device if further drug therapy is desired.

In another embodiment of the invention, electrodes on substantially flatsubstrates, in embodiments, sheets that comprise stretchable and/orflexible electronics may deliver stimulation to the brain, patch ofexterior skin, neural bundles, internal organs, and the like. Higherdensity electrodes (such as <1 cm spacing) may be enabled by reducingwiring complexity, including communications facilities with eachelectrode or to groups of electrodes, by including amplification andmultiplexing capabilities within array of electrodes, and the like.

Other embodiments of the invention, involve endoscopic imaging deviceshaving improved design efficiencies in terms of power and volume.Embodiments of the present invention incorporate conformal, curvilinearelectronic components for the purpose of volume reduction, imagingenhancement, and increased functionality.

It will be appreciated that the approach of the embodiment describedbelow may be applied to conventional tubular endoscopy devices andcapsule endoscopy devices, as well as any device utilizing the hereindescribed curved focal plane arrays of photodetectors that are comprisedin a CMOS imager. It should be noted that such curved focal plane arrayscan be utilized in conjunction with any embodiment described herein andthat all other embodiments described herein including those related tothe circuitry including and the elements thereof are intended to beutilized as applicable in the endoscopy embodiment described below.Curved silicon optical sensor arrays have significant advantages overconventional planar arrays. These advantages include a reduced number ofoptical elements, reduced aberrations including astigmatism and coma,and increased off-axis brightness and sharpness.

In embodiments of the invention, an endoscopy device is fitted with acurvilinear array of sensors and/or transducers, e.g., on the exteriorsurface thereof, thereby reducing the required volume of the device.This approach is particularly advantageous in reducing the overall sizeof an endoscopy device, allowing integration of additional diagnosticand therapeutic and/or sensing functionality including any describedherein an the following examples, ultrasound, pressure sensing,temperature sensing, pH, chemical sensing, targeted drug delivery,electrocautery, biopsy, laser, and heating), and increasing theallowable battery size. Increasing the power storage of a capsuleendoscopy device can lead to improvements in image quality, imagecompression, transmission rate, number of images captured, and theintensity of illumination produced by the LEDs.

In embodiments of the invention, a capsule endoscopy device and itsinternal circuitry are both made flexible and/or stretchable from any ofthe materials described for substrates including other biocompatiblematerials apparent to those skilled in the art. Such aflexible/stretchable endoscopy device may have increased ease of motionalong the GI tract and also increased viable volume. In otherembodiments, the device may have a rigid capsule-like structure withelectronics conformally fitted in the inner and/or outer shell of thecapsule. The exposed surface—either a rigid ellipsoid shell or aflexible or stretchable layer—is fabricated from a material resistant tothe harsh digestive environment that the endoscopy device willencounter, but which is also is biocompatible and harmless to thepatient's internal anatomy. Other properties of biocompatibility of theouter surface are described herein.

The stretchable electronic components of the endoscopy device have beendescribed herein in connection with the discussion of circuitry in allembodiments. In embodiments, circuitry comprises sensing and imagingarrays for monitoring features that are inside of bodily cavities andlumen such as the GI tract. As described above, the functionality mayreside in circuitry comprising devices which may comprise device islandsor vice verse. The islands house required circuitry and areinterconnected mechanically and electronically via interconnects such asthose described herein. The interconnects, in turn, preferentiallyabsorb strain and thus channel destructive forces away from the deviceislands. They provide a mechanism by which the integrated circuits canstretch and flex when a force is applied. The device islands andinterconnects may be integrated into the casing or encapsulating shellof the endoscopy device by transfer printing, as described below.Encapsulation of electronic devices and system/device interconnectintegration can be performed at any of a number of stages in thisprocess.

As with other embodiments described herein, the circuitry used in theelectronic devices may comprise standard IC sensors, transducers,interconnects and computation/logic elements. In embodiments, electronicdevices are typically made on a silicon-on-insulator (SOI) wafer inaccordance with a circuit design implementing the desired functionality.Semiconductor devices may be processed on suitable carrier wafers whichprovide a top layer of ultrathin semiconductor supported by an easilyremoved layer (eg. PMMA). These wafers are used to fabricateflex/stretch ICs by standard processes, with particular island andinterconnect placement being tailored to the requirements of aparticular application. “Ultrathin” refers to devices of thin geometriesthat exhibit extreme levels of bendability. They are typically less than10 μm in thickness.

The above discussions of fabrication of circuitry applies to endoscopyembodiments. However, the following discussion will describe a transferstep for embodiments related to endoscopy (but not necessarily limitedthereto). In such embodiments, the circuitry is primarily used toenhance the imaging system of the device.

Imaging with a curved optical sensor array (instead of a planar array)is used in conjunction with a lens, illuminating LEDs, battery,computing unit, antenna and a radio transmitter. Wired telemetry is usedfor conventional tube endoscopy. A passive or active matrix focal planearray is fabricated using one of the stretchable processing techniquesdescribed above. The array includes single-crystal siliconphoto-detectors and current-blocking p-n junction diodes. Imagescaptured using the array are minimally processed by onboard computingand transmitted (wired or wireless) to an external receiver for furtherprocessing.

The focal plane array described below could be considered part of anyimaging facility described above. The individual photo detectors may benetworked via interconnect systems in accordance with the presentinvention. These devices are found on islands and are connected byinterconnects such as those interconnects described herein. Inembodiment, films of polyimide support certain regions and encapsulatethe entire system. Such a focal plane array can thus be incorporatedinto the endoscopy device.

FIG. 16 illustrates the process of making a such focal plane array. Thefirst step is fabricating the necessary circuitry 1000E, which in thisembodiment is a focal plane array, is the creation of a suitablegeometric transfer stamp to facilitate this process. In this embodiment,the circuitry is represented herein as 1000E (although it should beunderstood that is contemplated that this circuitry 1000E relates to andmay be used with other circuitry embodiments described herein).

At Step 1600A, an appropriate stamp (also referred to as transferelement) 240E is created by casting and curing poly(dimethylsiloxane)(PDMS) in the gap between opposing convex and concave lenses withmatching radii of curvature (1621E and 1622E respectively). The radiusof curvature should reflect the optimal parabolic curvature useful for anon-coplanar imager. At step 1600B, the cured curved transfer element240E (the removal of which from lenses stamping mechanism not shown) canbe stretched using a specially designed mechanism which provides outwardradial forces (in embodiments equal outward forces) along the rim of thestamp to create the planar pre-strained geometric transfer element. Thetransfer element should return to its initial size when relaxed.Transfer element 240E should also be large enough in its planarconfiguration to contact the entire area of electronic device islands onthe donor substrate.

A component of the circuitry 1000E in this embodiment is the processedelectronic devices joined by interconnects 1020E. At step 1600C, thecircuitry 1000E is brought into contact with the planar transfer element240E, which adheres to the former via sufficiently strong van der Waalsinteractions. The transfer element 240E is peeled back, thereby removingthe focal plane array, i.e., circuitry 1000E, from its handle wafer1626, shown at 1600D. After the focal plane array 1000E is removed fromthe handle wafer, the tension in the stamp is released and thecontacting layers, i.e., the focal plane array and the stamp, both takeinitial geometric form of the stamp (shown at 1600E). The focal planearray 1000E compresses and the networked interconnects 1020E of thearray buckle to accommodate the strain. The buckled focal plane array1000E is then transferred to its final substrate (shown in steps1600F-H) which has a matching radius of curvature and is also incommunication with the battery, antenna and a radio transmitter viaelectrical contacts. This transfer occurs by contacting both surfacesand is aided by the use of a photocurable adhesive. The adhesiveprovides sufficient attraction such that when the PDMS stamp is removed,it releases the curvilinear array of photodetectors onto the imagingsystem port. The curved focal plane array is then connected to the restof the imaging electronic components via electrode contact pads on theouter perimeter of the array.

In another embodiment shown in FIG. 16A, and endoscopy device 1680Ecomprising power 300E in the form of a battery, processing facility1200E, and data transmission facility 1500E is shown. Step 1601A showsconvex focal plane array 1000E that is adhered to the outer shell of theendoscopy device 1680E by, for example, a geometric transfer stamp 245E.After lifting the focal plane array off the handle wafer with the planarpre-strained PDMS (as described in connection with previous FIG. 16), itcan be relaxed and directly deposited onto the distal end of theendoscopy device 1680E, which is provided with a receiving substrate246E having, for example, a photocurable adhesive. After deposition ontothe endoscopy device 1680E (status shown as 1601B), electrical contactsare made from the array 1000E to the internal circuitry of the endoscopydevice 1680E. At 1601C, all of the exposed circuitry can be sealed witha suitable polymer and/or metal layer (eg. parylene, polyurethane,platinum, gold) 247E.

Micro-lens arrays may be required for such optical array systems.However, with proper illumination and negligible distance between theoptical array and the surface being imaged (e.g. near field imaging),this requirement may be nullified.

In yet another embodiment, a focal plane array, also referred to ascircuitry 1000E (as described above) is conformally wrapped around anendoscopy device such that it points in an outward radial direction fromthe long axis of the device. This is achieved by completing the sameplanar stretchable processing steps mentioned above and transferring thecircuit with a different specialized polymeric stamp. The transfer stampmay take the form of a planar rectangular strip. Each polymeric strip ispre-strained by thermal expansion (heat to around 160° C.) or byapplying uniform radial strain. This pre-strained polymer is thenpositioned in direct contact with the processed focal array. Theelastomer is subsequently peeled back to release the array from itshandle wafer. The stamp is then relaxed via cooling to room temperatureor gradual release of the mechanically induced strain. Release of thisstrain causes the elastomer to return to its initial shape, which inturn forces the device islands of the array to draw closer. Inembodiments, the interconnects are forced to buckle, enabling stretchingand bending characteristics. In embodiments, the area upon which thearray is meant to adhere is pre-treated with a photo-curable adhesive.Alternatively, a layer of PDMS may be used to enhance adhesion.

FIG. 16B details an embodiment of the process for transferring circuitryto the endoscopy device. The transfer is achieved by stamping the planararray of device islands and interconnects onto a curvilinear surfacesuch as an endoscopic device 1680E. 1602A shows the endoscopy devicehaving a thin PDMS shell or adhesive outer layer 250E. 1602B shows thecircuitry 1000E on a carrier substrate 201E. 1602C shows the step ofrotating the endoscopic device 1680E around a single revolution over thesubstrate 201E containing planar array of device islands, the array ofphotodetectors and interconnects will preferentially adhere to thesurface of the endoscopy device 1680E in a curvilinear manner as shownin Step 1602D.

In another embodiment, micro-lens arrays may be required for optimalfocusing and image quality. However, with proper illumination andnegligible distance between the optical array and the surface beingimaged, this requirement may be nullified. In the case where micro-lensarrays are required, they may be created directly as the encapsulatinglayer of the photodetector arrays during stretchable processing. Theymay also be stamped on after the endoscopic devices are made. Thisoptical array is then encapsulated and electronically integrated withthe rest of the endoscopic device in the following manner: electronicdevices which have been processed for stretching, can be picked up witha planar pre-strained PDMS stamp. The pre-strained PDMS stamp is thenrelaxed and brought into contact with the acceptor substrate fortransfer printing. This acceptor surface may be the surface of theendoscopy device, said surface coated with a thin PDMS layer, or aseparate thin appropriately shaped PDMS layer that may later be wrappedaround the endoscope. In the case where the devices are facing outwardson the endoscopy device substrate, they may be encapsulated (while intheir compressed state) with another layer of PDMS, or a liquid layer ofPDMS followed by an upper layer of solid PDMS to make a fluidencapsulation. Other materials/methods may also be applied. In the casewhere the devices are facing outwards on the endoscopy device substrate,they may be electrically externally interfaced at conductive pads thatshould be designed to be located at a convenient location. Anisotropicconductive film (ACF) connectors can be used to interface to theseconductive pads, by pressing and heating the film onto the pads.

In the case where the devices are fully encapsulated or facing inwards,they may be electrically externally interfaced by first removing part ofthe encapsulating polymer over the conductive pads through wet or drychemical etching, or physical mechanical removal of material, includingbut not limited to drilling. At this point, the ACF may be incorporated.Alternatively, the stretchable electronics may be electricallyinterfaced to an ACF prior to the transfer or encapsulation process.

In embodiments, circuitry 1000E may include a flexible LED array on theouter surface of the endoscopy device 1680E, as shown in FIG. 17. Suchan array provides illumination required for optical image capture. Arepresentative process for creating a flexible LED system is as follows:

LEDs are made from quantum well (QW) structures on a GaAs substrate. Inbetween the GaAs substrate and the QW structure is an AlAs sacrificiallayer. The QW structure is etched with reactive ion etching (RIE) todown to the sacrificial layer to form isolated square islands which maybe in the range of, for example, 10-1000 μm on an edge. A partialrelease/undercut of the islands with HF etching is performed.Photoresist is spun onto the substrate and patterned to form squaresaround the corners of the islands, to serve as anchors. A full HFrelease etch is performed to free the islands from the GaAs bulksubstrate; the photoresist anchors prevent the islands from floatingaway during etch, rinse and dry steps. An elastomeric stamp (for examplePDMS) is used to pick up the islands and transfer them to anothersubstrate. The transfer may be done in multiple steps, picking up afraction of the GaAs islands at a time, to rearrange them geometrically.The substrate onto which the islands are transferred for furtherprocessing may be a layer of PET (polyethylene plastic) on a glasssubstrate that can be later peeled off, or a layer of polyimide on topof a PMMA (polymethylmethacrylate) sacrificial layer, or a layer of PDMSetc. Parts of the LED islands are then patterned and wet etched so thatthe bottom n-type contact is exposed; this may be done with, forexample, a H3PO4+H2O2 combination. Parts of the islands are unetched sothat the upper p-type material can be contacted electrically as well.Next, a planarization layer of polyimide is spun on, patterned so thatvias extend down to the p and n type contact regions of the device. Thinfilm wires are deposited and patterned such that the wires to the p-typeregions run in one direction, and the wires to the n-type regions run inan orthogonal direction. One of the other wires should have a gap so asnot to cross-circuit. This gap is bridged by spinning anotherplanarization layer thereover and patterning it with vias to each sideof the gap, and metal is patterned over the planarization layer to makethe connection. Another passivation layer is spun on top, and the entirestack is etched so that the bridges and islands remain encapsulated withpolymer but the intervening areas are completely etched away. Thisallows the bridges to be flexible. The PMMA sacrificial layer isundercut, or the PET layer is peeled off, and the entire sheet withcircuits may be picked up again by PDMS stamp, and flipped over. Thebackside of the lower polyimide, or bottom of the circuits, is coatedwith Cr/SiO2; coating of the bridges is avoided by using a shadow maskevaporation procedure. The samples are subjected to a UV ozone treatmentto impart dangling bonds to the SiO2, facilitating formation of covalentbonds with the next substrate to which the circuits are transferred.This final substrate may be thermally or mechanically pre-strained PDMS,such that after transfer, the strain is relaxed and the devices movecloser together and the bridges pop up and buckle to accommodate thestrain.

The stretchable LED array is transferred to the endoscopy device in amanner similar to that of the cylindrical optical sensor array. It isthen encapsulated and integrated at the device level according to themethods described herein in connection with the micro-lens array. FIG.17 shows an endoscopy device 1680E wherein circuitry 1000E comprises andarray of photodetector and array of LED's (individually shown as 1030E.The LED array may utilize processing 1200E in the form of a logic deviceso that it only illuminates areas of interest during the operation andcan be turned off when not in use as a power-saving mechanism. Devicealso includes a data transmission facility which includes RF antenna1502 to wireless communicate with external devices.

In another embodiment of the present invention, the endoscopy device isequipped with an array of sensors which can be selected from thoseherein including those in connection with the discussion of 1100. Saidsensors working in conjunction with circuitry 1000E to monitor pH, thepresence of chemicals, and/or enzyme activity. IN embodiments, the datacollected by this sensor array is processed by local computing devicesand transmitted via RF antenna or wired telemetry to an externalreceiver for further analysis.

At least some of the sensors in the array may comprise an ion-sensitivefield effect transistor (ISLET), which generate data relating to changesin ion concentration. The output signals are typically a voltage and/orcurrent difference, the magnitude of which varies with the change ofsensed ion (eg. hydronium) and/or enzyme. Other types of chemicalsensors may be also or alternatively be utilized.

Another embodiment of the present invention relates to a capsuleendoscopy device with a plurality of electronic components conformallyfitted to the inside and/or outside walls of the capsule shell in orderto conserve space. Conformal components are created by first performingstretchable processing on suitable materials as described herein. Thebasic components of such an endoscopy device include a passive or activematrix focal plane array, lens, illuminating LEDs, battery and telemetrydevices (antenna and a radio transmitter). Optional components mayinclude sensors described herein including ultrasound transducers,pressure sensors (eg. silicon-based devices utilizing piezo-resistive orcapacitive sensing mechanism, polymer-based sensors, and/or opticallybased sensors that measure physical deflections), temperature sensors(eg. silicon band-gap temperature sensors, Pt resistance temperaturedevices), Ph/enzymatic/chemical sensors (eg. Islets, as discussedabove), targeted drug delivery components, electrocautery devices,biopsy devices, lasers, and heating devices. Components that benefitfrom contact with the GI wall and fluids (eg. chemical sensors, LED,optical arrays) are situated in such a manner as to communicate fluidlyor optically with the outer environment. This may be accomplished, forexample, by placing the devices conformally on the outer surface of thecapsule or through the use of electrodes which relay information fromthe outer region to the inside of the capsule. The remaining components(eg. battery, telemetry devices) are preferably located on the inside ofthe capsule.

Methods for creating stretchable focal plane arrays and incorporatingthem into a desired substrate are described above. The same methods usedto process and transfer focal plane arrays (stretchable processing) maybe employed for various single-crystal silicon based electronic devices(eg. antenna, RF transmitter, ISFET), with circuits being laid out (eg.using CAD tools) in a manner that accommodates mechanical deformationand stretching.

In embodiments where it is desired to incorporate heterogeneousintegrated circuits (non-silicon based devices), a slightly differentapproach may be employed. When creating a device that requiresheterogeneous integration (eg. LEDs), circuits are typically created ondifferent substrates. After stretchable processing, the electronicdevices are combined onto the same substrate using stamping methodspreviously described. This substrate may be the final destination of thedevices (product integration) or may instead be intermediate (i.e. Arigid, flexible or stretchable material which will be incorporated intothe product at a later time). At this point interconnects may berequired to keep all of the heterogeneous components in electricalcommunication. These may be provided using soft lithography or anotherlow-impact, low-temperature-processing (<400° C.) method with accuratealignment (<5 μm). The integrated circuit is then appropriatelyencapsulated and system/device interconnect integration can be executedas described above in connection with the micro-lens array.

As mentioned above, materials for the substrate used in the embodimentsherein may be biocompatible. Such is the case with substrates includingouter coatings of endoscopy device. In addition to biocompatibility, anypart of the device housing that comes between the imager array and theobject being monitored is preferably transparent. Further, the materialin the outer shell of the endoscopy device facilitates easy travelthrough the GI tract. Examples of suitable biocompatible materials aregiven above.

It is to be understood that the housing of the device described abovemay also be the substrate and vice verse. Therefore, the skilled artisanwill appreciate that certain discussions related to the substrate'smaterial may—in certain embodiments—be understood as to apply to saidhousing.

It has been described herein in connection with embodiments of theinvention that substrate can be fitted with circuitry comprising anarray sensors and that said sensors could comprise pressure sensors.Circuitry can also comprise processing 1200 and 1200A, data collection1300, amplifiers 1400, and data transmission 1500, among othercapabilities. Therefore, another embodiment will be described thatfacilitates a quantitative examination of tissue based on palpation. Inembodiments, the device is configured for self examination. The deviceis particularly suited for breast self-examinations; however, it will beappreciated that notwithstanding the following disclosure of anexemplary embodiment, the device and methods disclosed in connectionwith this exemplary embodiment apply to examinations of a variety oftissues and areas of the body, and such examination need not only bebased on palpation.

Such an apparatus comprises a conformable and stretchable polymer fittedwith an array of pressure transducers which remain operativenotwithstanding stretching and bending of the body. The polymersubstrate may cover a portion or the entire surface of the tissue and isused to measure the mechanical stiffness of the tissue at multiplediscrete points. Pressure transducers coupled with processing facilitycan measure the mechanical stiffness of the tissue in response to knownstrains exerted on the surface of the tissue during palpation. As withother embodiment of the invention, the electronic devices of thecircuitry may apparatus may comprise multiplexors, data acquisition andmicroprocessor circuits, which are connected via electronics wiring tothe sensory circuitry covering the polymer substrate. Detection ofabnormally hard regions of the tissue begins by first pressing the arrayof pressure transducers to the surface of the body part, for example, abreast. In embodiments, the device is fitted over the entire surfacearea of the body part (for example the breast) and as such a profile ofthe body-part stiffness can be mapped with high spatial resolution.

Embodiments of the present invention determine the presence and spatialextent of abnormally stiff legions of biological tissue, discriminatebetween relative stiffness of healthy and cancerous tissue, andfacilitate immediate and localized therapeutic measures if appropriate.Because the mechanical properties of breast tissue are intrinsicallyheterogeneous, the present invention may be used regularly over time toprecisely map the healthy state of the examined tissue thereby enablingthe detection of structural abnormalities and/or deviations over time.

Embodiments of the present invention involve an instrumented polymermembrane fitted with flexible and stretchable electronic sensor andimaging arrays for measuring the material, mechanical, and/or opticalproperties of biological tissue. The invention utilizes flexible andstretchable circuitry suited for measuring parameters such astemperature, pressure and electrical conductivity of biological tissues.More specifically, the breast region is one area of interest for suchtissue interrogation. The electronic components may be arranged inislands, which house required circuitry and are interconnectedmechanically and electronically via interconnects. The interconnects, inturn, preferentially absorb strain and therefore enable the sensorarrays to withstand extreme stretching and conform to non-uniform shapesof biological tissues. The device islands and interconnects may beintegrated into the device by transfer printing, as described below.Encapsulation of electronic devices and system/device interconnectintegration can be performed at a number of stages in this process.

As decried amply herein, the arrays of devices, which may include one ormore electronic devices and/or device components described herein (eg.pressure, light and radiation sensors, biological and/or chemicalsensors, amplifiers, A/D and D/A converters, optical collectors,electro-mechanical transducers, piezo-electric actuators), connected toa buffer and also to an amplifier are laid out in a device “island”arrangement. The device islands are ˜50 μm×50 μm 2 squares, most ofwhich. Some islands accommodate active matrix switches and A/Dconverters, and some islands accommodate logic circuitry capable ofreading in digital signals and processing them, and are capable ofoutputting data or storing data in memory cells. The circuits on theseislands are configured and designed such that preferably only about one,but not more than about 100 electrical interconnections are requiredbetween any two device islands. Circuitry is made and applied accordingthe methods described above, including in the manner described for adevice island arrangement of devices.

FIG. 18 shows an embodiment of the invention adapted for the humanbreast. In embodiments of the invention, a conformable polymericmembrane 200T in the shape of a single human breast 2040T. Applied tothe membrane 200T is circuitry 1000T comprising sensor and/or imagingarrays based on, for example, complementary metal-oxide semiconductor(CMOS) technology. In embodiments, the array(s) 1000T are physicallyintegrated into the surface of the polymeric breast-shaped membrane 200Tsuch as (poly)dimethylsiloxane (PDMS). This stamping procedure may bedone by a transfer printing process defined herein. As described herein,arrays 1000T can be made of CMOS devices, which offer a variety ofsophisticated sensing, imaging, and therapeutic functions, including(but not limited to) pressure sensing, light imaging, and trans-dermaldrug delivery. The device arrays 1000T are designed to withstandstretching and bending by the use of effective circuit layout andinterconnect designs as described herein.

In embodiments, the tissue screener may be created in the form of a bra275T or integrated into a bra.

Embodiments may include circuitry/array 1000T that comprises arrayedpressure sensors. As such electronic devices 1010T can include pressuresensor. Each pressure sensor island comprises a flexible diaphragmmembrane, which can record changes in capacitance in response todeflection. The pressure sensors can be made of a series ofpiezoresistive strain gauges, and/or conductive polymers. Eachelectronic device may contain an amplifier and A/D transistors toprovide local signal processing on each island. The sensor islands areencapsulated with a thin layer of polymer (˜100 μm thick) to protect theinterconnects and the circuitry. The surface containing the thin layeris positioned in direct contact with the breast tissue during theprocedure. The surface opposite the sensors can be fitted with anadditional polymer layer (300-500 μm thick) that forms as an enclosurewith an air-filled gap. Inflating this air-filled space by a knownamount (with a peristaltic pump) facilitates the application of knownstrains to the breast tissue. Therefore, breast tissue can be depressedby a fixed amount over its entire surface by inflating the air-filledspace, and the pressure at each location is recorded with pressuresensors.

In another embodiment, each device 1010T includes on-off switchtransistors that are coupled to said pressure sensors and activated oncepressure is applied. Using this on-off mechanism, the device candetermine which sensors have been pressed during sensing and communicatesuch to the user, via fro example, a graphical user interface on anexternal device, or visual means such as lighted areas were sensors havebeen either activated or not activated, or tactile indicators ofactuation. One key advantage of using a sensor array with on-offfeedback is that it alerts the user if any part of the sensor array hasnot been depressed in the case of manual force exertion onto the breast.Therefore, it eliminates the possibility of overlooking regions of thebreast during a manual examination. Thus in embodiments, each electronicdevice can provide feedback if the pressure sensing mechanism was notproperly activated during breast examination.

In another embodiment of the invention, the devices are anchored to thebreasts with straps similar to those of a 275T. Thus in use, the usercan wear the apparatus like a bra. In embodiments, the device has a port(not shown) for connecting to an external processing facility 1200A,which in FIG. 18 is depicted as residing in a laptop computer 1204T.Wireless communication is also possible and depicted in the figure. Theexternal device can provide power and also receives data duringscreening. In embodiments, processing facility 1204T, is in electroniccommunication with the circuitry and is configured to detect that thebra is worn and prompts the user to start the breast exam. The outersurface of the device on the side opposite to the breast can be coveredwith a thin encapsulating layer of polymer as described in previousembodiments. The space between this outer surface and the surface of theapparatus can be air-sealed and filled with air using a peristaltic airpump. Filling this space with air enables uniform pressure to be appliedalong the entire surface of the breast, which in turn provides controlover how much strain is applied to the breast.

In another embodiment of the invention, the stretchable material 200Tcomprises circuitry 1000T having an array of ultrasound transducers (eg.piezoelectric crystals). Each device 1010T comprises a receiver thatsenses acoustic reflections generated by a source emitter that sendsacoustic waves through the tissue at megahertz frequencies. Thisembodiment can be combined with other sensors mentioned herein,including, pressure sensors to further locate and image abnormal regionsof breast tissue. As with all embodiments herein, the sensors can be inelectronic communication with the other facilities, electronic devices,components, and elements of the circuitry or external devices includingprocessing facilities that receive the data from said sensors andprocess it according to the methods described herein, and further causeoutput devices to generate the output as described herein.

Circuitry 1000T could also comprise an array of infrared emitters anddetectors (eg. bolometer). The infrared wavelength is chosen to minimizethe ratio of healthy tissue absorption to cancerous tissue absorption.The emitters illuminate the breast and the detectors image theradiation. This embodiment can be combined and integrated with any ofthe aforementioned sensing concepts for increased accuracy.

Circuitry 1000T could also comprise an array of stimulating andrecording electrodes to produce a spatial map of electrical impedance ofthe tissue. The electrical conductivity and dielectric properties ofcancerous tissue may differ from those of healthy tissue. To detectchanges in electrical impedance induced by the presence of local cancertissue, a known AC current can be injected at a known location, andvoltage is recorded at a number of points defined by the array ofrecording electrodes. In this embodiment, the encapsulating layer ofpolymer covers everything except the contact regions of the electrodes.A photo-patternable polymer can be used to achieve this step.

Electrical impedance scanning provides data to enable a 3-D spatial mapof complex impedance and permittivity over a range of frequencies, whichcan be used as a sensing tool to predict the presence of abnormalcancerous cells deep within breast tissue. This embodiment can becombined and integrated with any of the aforementioned methods andconcepts for increased accuracy.

The data collected by the array of sensors can be stored for retrievaland/or transmitted to an external system for time-based tracking oftissue health.

In embodiments, the sensor data from the array 1000T of pressuretransducers can amplified and converted to digital form at the level ofeach sensor and then transmitted to a multiplexor. Alternatively, theanalog circuitry can be included at the level of each device 1010T andthe digital processing circuits can be housed off of the polymer. Oncethe data is collected from each point and transmitted to a computerterminal, the user may prompted that the examination is complete. Theuser may examine the data herself and/or send it to her doctor forfurther review (as an example).

Thus, in embodiments it will be apparent that the circuitry of thedevice is in electronic communication with a processing facilityconfigured to accept data from the device and cause output facility(previously discussed in connection with FIG. 1 as 300) to generate agraphical or otherwise visual presentation of data related to theexamination. For example, tissue maps as described herein may be createdfrom all sensor data disclosed herein and presented on output facility(as shown on 1204T). Textual and graphical data relating to the datagenerated by the circuitry may be presented to the user. The processingfacility may be configured to cause historical data generated by thecircuitry to be stored, aggregated, and presented in a variety of waysincluding daily, weekly, monthly, or any other useful interval readings,charts, reports, and the like.

Returning to the physical characteristics of the device itself, thedevice may be opaque such that the woman's breasts are not visible. Thisfeature can be achieved by adding opaque (e.g., black) dye to theelastomer prior to curing. In this embodiment, the array of sensorsremains in close contact with the breast without having to expose herbare breasts. Because of the biocompatibility of polymers like PDMS,this type of device can be fitted within a normal bra for convenience.

In one embodiment of the invention the electronics are integrated intoan elastomeric material which contours a breast. This shape isreproducible in different sizes depending on the breast size of theintended user. The process of creating the breast shaped device beginswith the creation of a first breast shaped mold. A second negativelyshaped mold is then made to match the curvature of the first. Anelastomeric material such as PDMS is poured between the two moulds tocreate a thin film (less than 2 mm). This layer is cured to create asolid breast shaped film of elastomeric material upon which theelectronics will be stamped by the transfer printing process describedabove. In order to accomplish this printing step, the elastomericmaterial is stretched into a flat plane and placed in contact with thealready “stretch processed” electronics. The electronics preferentiallyadhere to the surface of the elastomer either by Van der Waal forces orby chemical aided means. Subsequently, the elastomer with embeddedelectronics is relaxed and buckling occurs within the interconnects ofthe electronics array, enabling stretchability.

Further encapsulation and device integration may be required. This maybe done by connecting (manually or by electronic automation) anisotropicconductive films (ACF) to bond pads which are designed to be in aneasily accessible area on the stretchable electronic array (for exampleon its outer perimeter). This ACF connects the electronics embeddedelastomer to a device which is responsible for supplying power, relayinginformation of other tasks that require electrical contact.

In accordance with one or more embodiments, the stretchable electronicsare integrated directly onto a bra-like substrate. This may be achievedby coating a bra-like article with an elastomeric substrate (eg. PDMS)and adhering the above described stretchable electronic array to thenewly coated bra-like article.

Certain of the methods and systems described in connection with theinvention described (hereinafter referred to as the “Subject Methods andSystems”) may be deployed in part or in whole through a machine thatexecutes computer software, program codes, and/or instructions on aprocessor integrated with or separate from the electronic circuitrydescribed herein. Said certain methods and systems will be apparent tothose skilled in the art, and nothing below is meant to limit that whichhas already been disclosed but rather to supplement it.

The active stretchable or flexible circuitry described herein may beconsidered the machine necessary to deploy the Subject Methods andSystem in full or in part, or a separately located machine may deploythe Subject Methods and Systems in whole or in part. Thus, “machine” asreferred to herein may be applied to the circuitry described above, aseparate processor, separate interface electronics or combinationsthereof

The Subject Methods and Systems invention may be implemented as a methodon the machine, as a system or apparatus as part of or in relation tothe machine, or as a computer program product embodied in a computerreadable medium executing on one or more of the machines. Inembodiments, the processor may be part of a server, client, networkinfrastructure, mobile computing platform, stationary computingplatform, or other computing platform. A processor may be any kind ofcomputational or processing device capable of executing programinstructions, codes, binary instructions and the like. The processor maybe or include a signal processor, digital processor, embedded processor,microprocessor or any variant such as a co-processor (math co-processor,graphic co-processor, communication co-processor and the like) and thelike that may directly or indirectly facilitate execution of programcode or program instructions stored thereon. In addition, the processormay enable execution of multiple programs, threads, and codes. Thethreads may be executed simultaneously to enhance the performance of theprocessor and to facilitate simultaneous operations of the application.By way of implementation, methods, program codes, program instructionsand the like described herein may be implemented in one or more thread.The thread may spawn other threads that may have assigned prioritiesassociated with them; the processor may execute these threads based onpriority or any other order based on instructions provided in theprogram code. The processor, or any machine utilizing one, may includememory that stores methods, codes, instructions and programs asdescribed herein and elsewhere. The processor may access a storagemedium through an interface that may store methods, codes, andinstructions as described herein and elsewhere. The storage mediumassociated with the processor for storing methods, programs, codes,program instructions or other type of instructions capable of beingexecuted by the computing or processing device may include but may notbe limited to one or more of a CD-ROM, DVD, memory, hard disk, flashdrive, RAM, ROM, cache and the like. Nothing in this paragraph or theparagraphs below is meant to limit or contradict the description of theprocessing facility described herein and throughout.

A processor may include one or more cores that may enhance speed andperformance of a multiprocessor. In embodiments, the process may be adual core processor, quad core processors, other chip-levelmultiprocessor and the like that combine two or more independent cores(called a die).

The Subject Methods and Systems described herein may be deployed in partor in whole through a machine that executes computer software on aserver, client, firewall, gateway, hub, router, or other such computerand/or networking hardware. The software program may be associated witha server that may include a file server, print server, domain server,internet server, intranet server and other variants such as secondaryserver, host server, distributed server and the like. The server mayinclude one or more of memories, processors, computer readable media,storage media, ports (physical and virtual), communication devices, andinterfaces capable of accessing other servers, clients, machines, anddevices through a wired or a wireless medium, and the like. The methods,programs or codes as described herein and elsewhere may be executed bythe server. In addition, other devices required for execution of methodsas described in this application may be considered as a part of theinfrastructure associated with the server.

The server may provide an interface to other devices including, withoutlimitation, clients, other servers, printers, database servers, printservers, file servers, communication servers, distributed servers andthe like. Additionally, this coupling and/or connection may facilitateremote execution of program across the network. The networking of someor all of these devices may facilitate parallel processing of a programor method at one or more location without deviating from the scope ofthe invention. In addition, any of the devices attached to the serverthrough an interface may include at least one storage medium capable ofstoring methods, programs, code and/or instructions. A centralrepository may provide program instructions to be executed on differentdevices. In this implementation, the remote repository may act as astorage medium for program code, instructions, and programs.

If the Subject Methods and Systems are embodied in a software program,the software program may be associated with a client that may include afile client, print client, domain client, internet client, intranetclient and other variants such as secondary client, host client,distributed client and the like. The client may include one or more ofmemories, processors, computer readable media, storage media, ports(physical and virtual), communication devices, and interfaces capable ofaccessing other clients, servers, machines, and devices through a wiredor a wireless medium, and the like. The methods, programs or codes asdescribed herein and elsewhere may be executed by the client. Inaddition, other devices required for execution of methods as describedin this application may be considered as a part of the infrastructureassociated with the client.

The client may provide an interface to other devices including, withoutlimitation, servers, other clients, printers, database servers, printservers, file servers, communication servers, distributed servers andthe like. Additionally, this coupling and/or connection may facilitateremote execution of program across the network. The networking of someor all of these devices may facilitate parallel processing of a programor method at one or more location without deviating from the scope ofthe invention. In addition, any of the devices attached to the clientthrough an interface may include at least one storage medium capable ofstoring methods, programs, applications, code and/or instructions. Acentral repository may provide program instructions to be executed ondifferent devices. In this implementation, the remote repository may actas a storage medium for program code, instructions, and programs.

The Subject Methods and Systems described herein may be deployed in partor in whole through network infrastructures. The network infrastructuremay include elements such as computing devices, servers, routers, hubs,firewalls, clients, personal computers, communication devices, routingdevices and other active and passive devices, modules and/or componentsas known in the art. The computing and/or non-computing device(s)associated with the network infrastructure may include, apart from othercomponents, a storage medium such as flash memory, buffer, stack, RAM,ROM and the like. The processes, methods, program codes, instructionsdescribed herein and elsewhere may be executed by one or more of thenetwork infrastructural elements.

The methods, program codes, and instructions pertaining to the SubjectMethods and Systems described herein and elsewhere may be implemented ona cellular network having multiple cells. The cellular network mayeither be frequency division multiple access (FDMA) network or codedivision multiple access (CDMA) network. The cellular network mayinclude mobile devices, cell sites, base stations, repeaters, antennas,towers, and the like. The cell network may be a GSM, GPRS, 3G, EVDO,mesh, or other networks types.

The methods, program codes, and instructions pertaining to the SubjectMethods and Systems described herein and elsewhere may be implemented onor through mobile devices. The mobile devices may include navigationdevices, cell phones, mobile phones, mobile personal digital assistants,laptops, palmtops, netbooks, pagers, electronic books readers, musicplayers and the like. These devices may include, apart from othercomponents, a storage medium such as a flash memory, buffer, RAM, ROMand one or more computing devices. The computing devices associated withmobile devices may be enabled to execute program codes, methods, andinstructions stored thereon. Alternatively, the mobile devices may beconfigured to execute instructions in collaboration with other devices.The mobile devices may communicate with base stations interfaced withservers and configured to execute program codes. The mobile devices maycommunicate on a peer to peer network, mesh network, or othercommunications network. The program code may be stored on the storagemedium associated with the server and executed by a computing deviceembedded within the server. The base station may include a computingdevice and a storage medium. The storage device may store program codesand instructions executed by the computing devices associated with thebase station.

The computer software, program codes, and/or instructions pertaining tothe Subject Methods and Systems may be stored and/or accessed on machinereadable media that may include: computer components, devices, andrecording media that retain digital data used for computing for someinterval of time; semiconductor storage known as random access memory(RAM); mass storage typically for more permanent storage, such asoptical discs, forms of magnetic storage like hard disks, tapes, drums,cards and other types; processor registers, cache memory, volatilememory, non-volatile memory; optical storage such as CD, DVD; removablemedia such as flash memory (e.g. USB sticks or keys), floppy disks,magnetic tape, paper tape, punch cards, standalone RAM disks, Zipdrives, removable mass storage, off-line, and the like; other computermemory such as dynamic memory, static memory, read/write storage,mutable storage, read only, random access, sequential access, locationaddressable, file addressable, content addressable, network attachedstorage, storage area network, bar codes, magnetic ink, and the like.

The Subject Methods and Systems described herein may transform physicaland/or or intangible items from one state to another. The methods andsystems described herein may also transform data representing physicaland/or intangible items from one state to another.

The elements described and depicted herein and the functions thereof maybe implemented on machines through computer executable media having aprocessor capable of executing program instructions stored thereon as amonolithic software structure, as standalone software modules, or asmodules that employ external routines, code, services, and so forth, orany combination of these, and all such implementations may be within thescope of the present disclosure. Examples of such machines may include,but may not be limited to, personal digital assistants, laptops,personal computers, mobile phones, other handheld computing devices,medical equipment, wired or wireless communication devices, transducers,chips, calculators, satellites, tablet PCs, electronic books, gadgets,electronic devices, devices having artificial intelligence, computingdevices, networking equipments, servers, routers and the like.Furthermore, the elements depicted in the flow chart and block diagramsor any other logical component may be implemented on a machine capableof executing program instructions. Thus, while the foregoingdescriptions set forth functional aspects of the disclosed systems, noparticular arrangement of software for implementing these functionalaspects should be inferred from these descriptions unless explicitlystated or otherwise clear from the context. Similarly, it will beappreciated that the various steps identified and described above may bevaried, and that the order of steps may be adapted to particularapplications of the techniques disclosed herein. All such variations andmodifications are intended to fall within the scope of this disclosure.As such, the depiction and/or description of an order for various stepsshould not be understood to require a particular order of execution forthose steps, unless required by a particular application, or explicitlystated or otherwise clear from the context.

The Subject Methods and Systems, and steps associated therewith, may berealized in hardware, software or any combination of hardware andsoftware suitable for a particular application. The hardware may includea general purpose computer and/or dedicated computing device or specificcomputing device or particular aspect or component of a specificcomputing device. The processes may be realized in one or moremicroprocessors, microcontrollers, embedded microcontrollers,programmable digital signal processors or other programmable device,along with internal and/or external memory. The processes may also, orinstead, be embodied in an application specific integrated circuit, aprogrammable gate array, programmable array logic, or any other deviceor combination of devices that may be configured to process electronicsignals. It will further be appreciated that one or more of theprocesses may be realized as a computer executable code capable of beingexecuted on a machine readable medium.

The computer executable code may be created using a structuredprogramming language such as C, an object oriented programming languagesuch as C++, or any other high-level or low-level programming language(including assembly languages, hardware description languages, anddatabase programming languages and technologies) that may be stored,compiled or interpreted to run on one of the above devices, as well asheterogeneous combinations of processors, processor architectures, orcombinations of different hardware and software, or any other machinecapable of executing program instructions.

Thus, in one aspect, methods described above in connection with theSubject Systems and Methods and combinations thereof may be embodied incomputer executable code that, when executing on one or more computingdevices, performs the steps thereof. In another aspect, the methods maybe embodied in systems that perform the steps thereof, and may bedistributed across devices in a number of ways, or all of thefunctionality may be integrated into a dedicated, standalone device orother hardware. In another aspect, the means for performing the stepsassociated with the processes described above may include any of thehardware and/or software described above. All such permutations andcombinations are intended to fall within the scope of the presentdisclosure.

While the invention has been described in connection with certainpreferred embodiments, other embodiments would be understood by one ofordinary skill in the art and are encompassed herein.

All documents referenced herein are hereby incorporated by reference.

What is claimed is:
 1. An apparatus comprising: a substrate; circuitrydisposed on said substrate, said circuitry comprising: an array ofrecording electrodes receiving signals from a plurality of nerve sourceswhen at least a portion of said array of recording electrodes is inelectrical contact with said plurality of nerve sources; and an array ofstimulating electrodes; and a processing facility in electroniccommunication with said arrays of electrodes that receives said signalsfrom a plurality of nerve sources from said recording electrodes and isconfigured to determine a pattern of stimulation signals to be effectedby said array of stimulating electrodes.
 2. The apparatus of claim 1,wherein said electrical contact comprises physical contact.
 3. Theapparatus of claim 1, further comprising a multiplexer configured tomatch said signals from said nerve sources and cause said stimulatingelectrodes to dispatch a corresponding signal to a second plurality ofnerves.
 4. The apparatus of claim 1, further comprising a user interfaceto allow an operator to adjust said pattern of stimulation signals. 5.The apparatus of claim 1, wherein said substrate is an inflatable body.6. The apparatus of claim 5, wherein said inflatable body is a disk. 7.The apparatus of claim 1, wherein said pattern of stimulation signals isdynamically configurable.
 8. The apparatus of claim 1, wherein saidprocessing facility is further configured to generate data related tothe electrical conductivity of said nerve sources.
 9. The apparatus ofclaim 8, wherein said processing facility is in electronic communicationwith an output facility and causes said output facility to generate amap, said map being based on said data related to the electricalconductivity of said nerve sources.
 10. The apparatus of claim 1,wherein circuitry is encapsulated with a thin polymer layer.
 11. Theapparatus of claim 1, wherein circuitry is stretchable up to 300%. 12.The apparatus of claim 1, wherein said electrodes are located discretelyfrom one another.
 13. The apparatus of claim 1, wherein said circuitrycomprises stretchable electrical interconnects.
 14. The apparatus ofclaim 13, wherein said stretchable interconnects electrically connectsaid electrodes.
 15. The apparatus of claim 1, wherein said circuitrycomprises temperature sensors.
 16. The apparatus of claim 1, whereinsaid circuitry comprises contact sensors.
 17. The apparatus of claim 1,wherein said circuitry comprises pressure sensors.
 18. The apparatus ofclaim 1, wherein said substrate comprises a reservoir in communicationwith the surface of said substrate.
 19. The apparatus of claim 18,wherein said circuitry is configured to open valves operable to releasea drug contained within said reservoir.
 20. The apparatus of claim 19,wherein said circuitry causes the valves to release said drug in acontrolled manner.
 21. An apparatus comprising: an inflatable substrate;circuitry disposed on said substrate comprising an array of activedevices, said circuitry being configured to remain functional uponinflation of the substrate, said array comprising sensing devices fordetecting data indicative of a parameter associated with a tissue; aprocessing facility in electronic communication with said circuitry,receiving said data indicative of a parameter associated with saidtissue; and an output facility in electronic communication with saidprocessing facility, said processing facility configured to generateoutput data associated with said tissue and to cause said outputfacility to generate said output data.
 22. The apparatus of claim 21,wherein said substrate is stretchable.
 23. The apparatus of claim 21,wherein said circuitry is in conformal contact with said tissue.
 24. Theapparatus of claim 21, wherein said circuitry is encapsulated with athin polymer layer.
 25. The apparatus of claim 21, wherein saidcircuitry is stretchable up to 300%.
 26. The apparatus of claim 21,wherein said active devices are located discretely from one another. 27.The apparatus of claim 21, wherein said circuitry comprises stretchableelectrical interconnects.
 28. The apparatus of claim 27, wherein saidstretchable interconnects electrically connect said devices.
 29. Theapparatus of claim 21, wherein said sensing devices comprise temperaturesensors.
 30. The apparatus of claim 21, wherein said sensing devicescomprise contact sensors.
 31. The apparatus of claim 21, wherein saidsensing devices comprise pressure sensors.
 32. The apparatus of claim21, wherein said sensing devices comprise ultrasound emitters andreceivers.
 33. The apparatus of claim 32, wherein said processingfacility receives data generated by said sensing devices and produces animage of said tissue.
 34. The apparatus of claim 21, wherein saidsensing devices are configured to be in an active matrix.
 35. Theapparatus of claim 34, wherein said circuitry comprises at least one ofan amplifier and a logic circuit to operate said sensors in said activematrix.
 36. The apparatus of claim 21, wherein said apparatus furthercomprising a multiplexer.
 37. The apparatus of claim 36, wherein saidsubstrate is a balloon coupled with a catheter guide wire, and saidmultiplexer is located at the base of said guide wire.
 38. The apparatusof claim 21, wherein said processing facility is within said circuitry.39. The apparatus of claim 21, wherein said processing facility isseparate from said circuitry.
 40. The apparatus of claim 21, whereinsaid output data related to said tissue is a map.
 41. The apparatus ofclaim 40, wherein said map comprises a map of electrical activity ofsaid tissue.
 42. The apparatus of claim 21, wherein said output datacomprises data related to temperature heterogeneity present in arterialplaque.
 43. The apparatus of claim 21, wherein said output datacomprises an indication of plaque type.
 44. The apparatus of claim 21,wherein said circuitry comprises a therapeutic facility.
 45. Theapparatus of claim 44, wherein said therapeutic facility is configuredto ablate said tissue.
 46. The apparatus of claim 21, wherein saidcircuitry comprises light emitting electronics.
 47. The apparatus ofclaim 21, wherein said circuitry comprises an array of photodetectors incommunication with said processing facility.
 48. The apparatus of claim47, wherein said processing facility is configured to generate image ofsaid tissue and to cause said output facility to output an image. 49.The apparatus of claim 48, wherein said image is high resolution. 50.The apparatus of claim 47, wherein said circuitry is delivered via acatheter having a guide wire, and wherein said guide wire comprises alight source to provide light to said photodetectors.
 51. The apparatusof claim 50, wherein said light source is an optical fiber.
 52. Theapparatus of claim 21, wherein said tissue is a pulmonary vein.
 53. Theapparatus of claim 21, wherein said tissue is a septal wall of a heart.54. The apparatus of claim 21, wherein said tissue is an atrial surfaceof a heart.
 55. The apparatus of claim 21, wherein said tissue is aventricular surface of a heart.
 56. The apparatus of claim 21, whereinsaid substrate comprises reservoir in communication with the surface ofsaid substrate.
 57. The apparatus of claim 56, wherein said circuitry isconfigured to open valves on the substrate to release a drug containedwithin said reservoir.
 58. The apparatus of claim 57, wherein saidcircuitry causes the valves to release said drug in a controlled manner.59. A method of detecting parameters associated with a lumen in the bodyof an individual, said method comprising: a. inserting an un-inflatedballoon catheter into said lumen, said balloon catheter having astretchable balloon having stretchable circuitry applied thereto, thestretchable circuitry comprising sensing devices; b. directing saidsensing devices to be in an area of interest within said lumen; and c.inflating said balloon and causing said sensing devices to come intoconformal contact with surface of said area of interest within saidlumen.
 60. The method of claim 59, wherein said circuitry is stretchedup to 300% upon said inflation.
 61. The method of claim 59, wherein saidsensing devices are located discretely from one another.
 62. The methodof claim 59, wherein said circuitry comprises stretchable electricalinterconnects.
 63. The method of claim 62, wherein said stretchableinterconnects electrically connect said devices.
 64. The method of claim59, wherein said sensing devices comprise temperature sensors.
 65. Themethod of claim 59, wherein said sensing devices comprise contactsensors.
 66. The method of claim 59, wherein said sensing devicescomprise pressure sensors.
 67. The method of claim 59, wherein saidsensing devices comprise ultrasound emitters and receivers.
 68. Themethod of claim 59, further comprising utilizing said sensing devices togenerate data indicative of a parameter of said area of interest whensaid sensing devices are in conformal contact with said area ofinterest.
 69. The method of claim 68, utilizing said generated data toproduce an image of said area of interest.
 70. The method of claim 68,utilizing said generated data to produce a map of said area of interest.71. The method of claim 70, wherein said map comprises a data indicativeof the electrical activity of said area of interest.
 72. The method ofclaim 59, wherein said area of interest includes arterial plaque andfurther comprising utilizing said parameters to generate data related totemperature heterogeneity present in arterial plaque.
 73. The method ofclaim 59, wherein said area of interest includes arterial plaque andfurther comprising utilizing said parameters to generate data indicativeof plaque type.
 74. The method of claim 59, further comprisingdelivering a therapy to said area of interest based on data indicativeof said area of interest.
 75. The method of claim 74, wherein step ofdelivering a therapy includes abalating said area of interest.
 76. Themethod of claim 74, wherein step of delivering a therapy includesdelivering a drug to said area of interest.
 77. The method of claim 59,wherein said area of interest is a pulmonary vein.
 78. The method ofclaim 59, wherein said area of interest is a septal wall of a heart. 79.The method of claim 59, wherein said area of interest is an atrialsurface of a heart.
 80. The method of claim 59, wherein said area ofinterest is a ventricular surface of a heart.
 81. A method of detectingparameters associated with a lumen in the body of an individual, saidmethod comprising: a. inserting an un-inflated balloon catheter intosaid lumen, said balloon catheter having a stretchable balloon havingstretchable circuitry applied thereto, the stretchable circuitrycomprising sensing devices; b. directing said sensing devices to be inan area of interest within said lumen; and c. inflating said balloon andcausing said sensing devices to come into partial sensing contact withsaid area of interest within said lumen.
 82. A method of detecting aparameter of a tissue, comprising: a. placing an array of active sensingdevices in conformal contact with said tissue, said array comprisingstretchable circuitry; b. generating data with said sensing devices; andc. determining said parameter from said generated data.
 83. The methodof claim 82, wherein said circuitry is stretched up to 300%.
 84. Themethod of claim 82, wherein said sensing devices are located discretelyfrom one another.
 85. The method of claim 82, wherein stretchableinterconnects electrically connect said sensing devices.
 86. The methodof claim 82, wherein said sensing devices comprise temperature sensors.87. The method of claim 82, wherein said sensing devices comprisecontact sensors.
 88. The method of claim 82, wherein said sensingdevices comprise pressure sensors.
 89. The method of claim 82, whereinsaid sensing devices comprise ultrasound emitters and receivers.
 90. Themethod of claim 82, wherein said parameter comprises an image of saidtissue.
 91. The method of claim 90, wherein said image comprises a dataindicative of the electrical activity of said tissue.
 92. The method ofclaim 82, wherein said parameter comprises temperature heterogeneitypresent in arterial plaque.
 93. The method of claim 82, wherein saidparameter comprises plaque type.
 94. The method of claim 82, furthercomprising delivering a therapy to said tissue based on said parameter.95. The method of claim 94, wherein step of delivering a therapyincludes abalating said tissue.
 96. The method of claim 94, wherein stepof delivering a therapy includes delivering a drug to said tissue. 97.The method of claim 82, wherein said tissue is a pulmonary vein.
 98. Themethod of claim 82, wherein said tissue is a septal wall of a heart. 99.The method of claim 82, wherein said tissue is an atrial surface of aheart.
 100. The method of claim 82, wherein said tissue is a ventricularsurface of a heart.
 101. A tissue screening device, comprising: astretchable substrate conformable to the contour of an area of intereston a body; stretchable circuitry affixed to said substrate, saidcircuitry comprising an array of active devices; a processing facilityin electronic communication with said array of active devices; and anoutput facility in electronic communication with said processingfacility, wherein said processing facility is programmed to generateoutput data based on data generated by said array of active devices andto cause said output facility to display said output data.
 102. Thedevice of claim 101, wherein said substrate is inflatable.
 103. Thedevice of claim 101, wherein said substrate is affixed to a bra. 104.The device of claim 101, wherein said circuitry is in conformal contactwith said area of interest.
 105. The device of claim 101, wherein saidcircuitry is encapsulated with a thin polymer layer.
 106. The device ofclaim 101, wherein said circuitry is stretchable up to 300%.
 107. Thedevice of claim 101, wherein said active devices are located discretelyfrom one another.
 108. The device of claim 101, wherein said circuitrycomprises stretchable electrical interconnects.
 109. The device of claim108, wherein said stretchable interconnects electrically connect saiddevices.
 110. The device of claim 101, wherein said active devicescomprise sensing devices.
 111. The device of claim 110, wherein saidsensing devices comprise temperature sensors.
 112. The device of claim110, wherein said sensing devices comprise contact sensors.
 113. Thedevice of claim 110, wherein said sensing devices comprise pressuresensors.
 114. The device of claim 113, wherein said active devicescomprise an on-off switch coupled to said pressure sensor to indicatewhether said pressure sensor has been activated.
 115. The device ofclaim 110, wherein said sensing devices comprise ultrasound emitters andreceivers.
 116. The device of claim 115, wherein said processingfacility receives data generated by said sensor devices and produces animage of said tissue.
 117. The device of claim 101, wherein saidprocessing facility is within said circuitry.
 118. The device of claim101, wherein said processing facility is separate from said circuitry.119. The device of claim 101, wherein said output data comprises acontour map of said area of interest.
 120. The device of claim 101,further comprising a storage facility in communication with saidprocessing facility.
 121. The device of claim 120, wherein saidprocessing facility causes at least one of data generated by said activedevices and said output data to be stored in said storage facility. 122.The device of claim 121, wherein said processing facility generatesoutput data related to said stored data.
 123. The device of claim 120,wherein said processing facility causes at least one of data generatedby said active devices and said output data to be aggregated.
 124. Thedevice of claim 123, wherein said processing facility generates outputdata related to said aggregated data.
 125. A method of examination forcancerous or suspicious tissue, comprising the steps of: providing asubject with a wearable device conforming to an area of interest onsubject's body, said wearable device comprising a stretchable array ofpressure sensors; exerting a manual force on said wearable devicesufficient to activate said array of pressure sensors; receiving datafrom said pressure sensors; and characterizing the tissue in the area ofinterest based on said received data.
 126. The method of claim 125,further comprising instructing said subject to exert said manual force.127. The method of claim 125, wherein said wearable device isinflatable.
 128. The method of claim 125, wherein said wearable deviceis affixed to a bra.
 129. The method of claim 125, wherein said wearabledevice is a sheet.
 130. An endoscopic device, comprising: a housing;curvilinear circuitry that is at least one of mounted to and mountedwithin said housing, said circuitry comprising a focal plane arraygenerating visual data; a transmission facility in electroniccommunication with said circuitry configured to wirelessly transmit saidvisual data; and an output facility receiving and displaying said visualdata.
 131. The device of claim 130, wherein said circuitry isstretchable.
 132. The device of claim 130, wherein said housing is acapsule.
 133. The device of claim 132, wherein said circuitry,transmission facility, and said output facility are mounted within saidcapsule.
 134. The device of claim 130, wherein said housing is locatedat a tip of said endoscopic device.
 135. The device of claim 130,wherein said circuitry further comprises light emitting electronics.136. The device of claim 135, wherein said circuitry is configured toilluminate select portions of the light emitting electronics.
 137. Thedevice of claim 130, wherein said circuitry is stretchable.
 138. Thedevice of claim 130, wherein said circuitry is affixed to an exteriorsurface of said housing.
 139. The device of claim 130, wherein saidcircuitry is affixed to an interior surface of said housing.
 140. Thedevice of claim 130, wherein said circuitry further comprises sensingdevices.
 141. The device of claim 140, wherein said sensing devicescomprise sensors capable of generating data related to enzymaticactivity.
 142. The device of claim 140, wherein said sensing devicescomprise sensors capable of generating data related to chemicalactivity.
 143. The device of claim 130, wherein said endoscopic devicecomprises a temperature sensor.
 144. The device of claim 130, whereinsaid endoscopic device comprises a contact sensor.
 145. The device ofclaim 130, wherein said endoscopic device comprises a pressure sensor.146. The device of claim 130, wherein said circuitry is configured to bein conformal contact with a tissue.
 147. The device of claim 130,wherein said circuitry is encapsulated.
 148. The device of claim 130,wherein said circuitry is stretchable up to 300%.
 149. The device ofclaim 130, wherein said endoscopic device comprises an ultrasoundemitter and receiver.
 150. The device of claim 130, wherein saidcircuitry comprises sensing devices and a processing facility receivingdata from said sensing devices, said processing facility in electroniccommunication with said output facility.
 151. The device of claim 150,wherein said processing facility causes said output facility to displayinformation related to data generated by said sensing devices.
 152. Thedevice of claim 130, further including a processing facility within saidcircuitry.
 153. The device of claim 130, further including a processingfacility separate from said circuitry.
 154. The device of claim 130,wherein said visual data is an image.
 155. The device of claim 130,wherein said visual data is a map.
 156. A configurable sheet ofelectronic devices, a substantially flat substrate, stretchablecircuitry on said substrate, said circuitry containing an array ofelectronic devices in electronic communication with one another; and aprocessing facility capable of polling said array of electronic devicesto determine a first set of information related to the identity andlocation of each electronic device in said array, said processingfacility configured to adjust the operation of said array based uponinformation related to a second set of information related to theidentity and location of each electronic device in said array.
 157. Theconfigurable sheet of claim 156, wherein the second set of informationis received after said circuitry is reshaped.
 158. The configurablesheet of claim 157, wherein said reshaping is caused by cutting saidcircuitry.
 159. The configurable sheet of claim 156, wherein said arrayof electronic devices comprise sensor devices.
 160. The configurablesheet of claim 159, wherein said sensor devices generate data of atissue of interest when said sheet is at least one of partial electricalcontact and partial conformal contact with said tissue of interest.